An insight into fluorescence and magnetic resonance bioimaging using a multifunctional polyethyleneimine-passivated gadocarbon dots nanoconstruct assembled with AS1411.

A nanoassembly of PEI-passivated Gd@CDs, a type of aptamer, is presented which was designed and characterized in order to target specific cancer cells based on their recognition of the receptor nucleolin (NCL), which is overexpressed on the cell membrane of breast cancer cells for fluorescence and magnetic resonance imaging and treatment. Using hydrothermal methods, Gd-doped nanostructures were synthesized, then modified by a two-step chemical procedure for subsequent applications: the passivating of Gd@CDs with branched polyethyleneimine (PEI) (to form Gd@CDs-PEI1 and Gd@CDs-PEI2), and using AS1411 aptamer (AS) as a DNA-targeted molecule (to generate AS/Gd@CDs-PEI1 and AS/Gd@CDs-PEI2). Consequently, these nanoassemblies were constructed as a result of electrostatic interactions between cationic Gd@CDs-passivated PEI and AS aptamers, offering efficient multimodal targeting nanoassemblies for cancer cell detection. It has been demonstrated through in vitro studies that both types of AS-conjugated nanoassemblies are highly biocompatible, have high cellular uptake efficiency (equivalent concentration of AS: 0.25 µΜ), and enable targeted fluorescence imaging in nucleolin-positive MCF7 and MDA-MB-231 cancer cells compared to MCF10-A normal cells. Importantly, the as-prepared Gd@CDs, Gd@CDs-PEI1, and Gd@CDs-PEI2 exhibit higher longitudinal relaxivity values (r1) compared with the commercial Gd-DTPA, equal to 5.212, 7.488, and 5.667 mM-1s-1, respectively. Accordingly, it is concluded that the prepared nanoassemblies have the potential to become excellent candidates for cancer targeting and fluorescence/MR imaging agents, which can be applied to cancer imaging and personalized nanomedicine.

Biodegradable and biocompatible subcutaneous implants consisted of pH-sensitive mebendazole-loaded/folic acid-targeted chitosan nanoparticles for murine triple-negative breast cancer treatment.

BACKGROUND: Mebendazole (MBZ) is a well-known anti-parasite drug with significant anti-cancer properties. However, MBZ exhibits low solubility, limited absorption efficacy, extensive first-pass effect, and low bioavailability. Therefore, multiple oral administration of high dose MBZ is required daily for achieving the therapeutic serum level which can cause severe side effects and patients' non-compliance. METHOD: In the present study, MBZ-loaded/folic acid-targeted chitosan nanoparticles (CS-FA-MBZ) were synthesized, characterized, and used to form cylindrical subcutaneous implants for 4T1 triple-negative breast tumor (TNBC) treatment in BALB/c mice. The therapeutic efficacy of the CS-FA-MBZ implants was investigated after subcutaneous implantation in comparison with Control, MBZ (40 mg/kg, oral administration, twice a week for 2 weeks), and CS-FA implants, according to 4T1 tumors' growth progression, metastasis, and tumor-bearing mice survival time. Also, their biocompatibility was evaluated by blood biochemical analyzes and histopathological investigation of vital organs. RESULTS: The CS-FA-MBZ implants were completely degraded 15 days after implantation and caused about 73.3%, 49.2%, 57.4% decrease in the mean tumors' volume in comparison with the Control (1050.5 ± 120.7 mm3), MBZ (552.4 ± 76.1 mm3), and CS-FA (658.3 ± 88.1 mm3) groups, respectively. Average liver metastatic colonies' number per microscope field at the CS-FA-MBZ group (2.3 ± 0.7) was significantly (P < 0.05) lower than the Control (9.6 ± 1.7), MBZ (5.0 ± 1.5), and CS-FA (5.2 ± 1) groups. In addition, the CS-FA-MBZ treated mice exhibited about 52.1%, 27.3%, and 17% more survival days after the cancer cells injection in comparison with the Control, MBZ, and CS-FA groups, respectively. Moreover, the CS-FA-MBZ implants were completely biocompatible based on histopathology and blood biochemical analyzes. CONCLUSION: Taking together, CS-FA-MBZ implants were completely biodegradable and biocompatible with high therapeutic efficacy in a murine TNBC model.

Effects of nanozeolite/starch thermoplastic hydrogels on wound healing.

BACKGROUND: Wound healing is a complex biological process. Some injuries lead to chronic nonhealing ulcers, and healing process is a challenge to both the patient and the medical team. We still look forward an appropriate wound dressing. MATERIALS AND METHODS: In this study, starch-based nanocomposite hydrogel scaffolds reinforced by zeolite nanoparticles (nZ) were prepared for wound dressing. In addition, a herbal drug (chamomile extract) was added into the matrix to accelerate healing process. To estimate the cytocompatibility of hydrogel dressings, fibroblast mouse cells (L929) were cultured on scaffolds. Then, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium-bromide assay test and interaction of cells and scaffolds were evaluated. For evaluating healing process, 48 male rats were randomly divided into four groups of four animals each (16 rats at each step). The ulcers of the first group were treated with the same size of pure hydrogels. The second group received a bandage with the same size of hydrogel/extract/4 wt% nZ (hydrogel NZE). The third group was treated with chamomile extract, and the fourth group was considered as control without taking any medicament. Finally, the dressings were applied on the chronic refractory ulcers of five patients. RESULTS: After successful surface morphology and cytocompatibility tests, the animal study was carried out. There was a significant difference between starch/extract/4 wt% nZ and other groups on wound size decrement after day 7 (P < 0.05). At the clinical pilot study step, the refractory ulcers of all five patients were healed without any hypersensitivity reaction. CONCLUSION: Starch-based hydrogel/zeolite dressings may be safe and effective for chronic refractory ulcers.

Double-walled microspheres loaded with meglumine antimoniate: preparation, characterization and in vitro release study.

OBJECTIVE: The objective of this study was to fabricate double-walled poly(lactide-co-glycolide) (PLGA) microspheres to increase encapsulation efficiency and avoid rapid release of hydrophilic drugs such as meglumine antimoniate. METHODS: In this study, double-walled and one-layered microspheres of PLGA were prepared using the emulsion solvent evaporation technique to better control the release of a hydrophilic drug, meglumine antimoniate (Glucantime®), which is the first choice treatment of cutaneous leishmaniasis. The effect of hydrophobic coating on microspheres' size, morphology, encapsulation efficiency and drug release characteristics was evaluated. Furthermore, the presence of antimony in meglumine antimoniate made it possible to observe the drug distribution within the microspheres' cross section by means of energy dispersive X-ray spectroscopy. RESULTS: Drug distribution images confirmed accumulation of the drug within the inner core of double-walled microspheres. In addition, these microspheres encapsulated the drug more efficiently up to 87% and demonstrated reduced initial burst and prolonged release compared to one-layered microspheres. These superiorities make double-walled microspheres an optimum candidate for sustained delivery of hydrophilic drugs. CONCLUSION: Double-walled microspheres provide some advantages over traditional microspheres overcoming most of their limitations. Double-walled microspheres were found to be more efficient than their corresponding one-layered microspheres in terms of encapsulation efficiencies and release characteristics.

A route toward fabrication of 3D printed bone scaffolds based on poly(vinyl alcohol)-chitosan/bioactive glass by sol-gel chemistry.

Among different methods for the fabrication of bone scaffolds, 3D printing has created great advances in tissue engineering and regenerative medicine owing to its ability to make objects mimicking native tissues. Thanks to its abundant availability, structural features, and favorable biological properties, chitosan (CS) hydrogel was selected to be used for preparation of the bone scaffolds. However, the 3D printing of CS-based hydrogels is still under early exploration. Knowing the fact that natural polymers are not so competent at holding large amounts of water, poly(vinyl alcohol) as the second polymer was employed. The novelty of the present research lies in the concept of employing sol-gel chemistry in order to attain proper viscosity and rheological behavior to give self-standing filaments of the polymer blends. Employing sol-gel reaction in the preparation of the hybrid hydrogels had the advantage of endowing shape fidelity to the polymer blend without any solidifying in the needle. The obtained organic-inorganic hybrids were directly printed and subsequently cross-linked. The best performance in terms of mechanical strength, cell viability, and bio-mineralization was observed for the 50:50 ratio. The in vitro cell culture and the bioactivity results showed that the printed scaffolds with this method have great potential in bone tissue engineering. Further, this method could be expandable to print other hydrogels with diverse applications such as implantable devices, soft robotics, etc.

Evaluation of the Morphological Effects of Hydroxyapatite Nanoparticles on the Rheological Properties and Printability of Hydroxyapatite/Polycaprolactone Nanocomposite Inks and Final Scaffold Features.

This study is focused on the importance of nanohydroxyapatite (nHA) particle morphology with the same particle size range on the rheological behavior of polycaprolactone (PCL) composite ink with nHA as a promising candidate for additive manufacturing technologies. Two different physiologic-like nHA morphologies, that is, plate and rod shape, with particles size less than 100 nm were used. nHA powders were well characterized and the printing inks were prepared by adding the different ratios of nHA powders to 50% w/v of PCL solution (nHA/PCL: 35/65, 45/55, 55/45, and 65/35 w/w%). Subsequently, the influence of nHA particle morphology and concentration on the printability and rheological properties of composite inks was investigated. HA nanopowder analysis revealed significant differences in their microstructural properties, which affected remarkably the composite ink printability in several ways. For instance, adding up to 65% w/w of plate-like nHA to the PCL solution was possible, while nanorod HA could not be added above 45% w/w. The printed constructs were successfully fabricated using the extrusion-based printing method and had a porous structure with interconnected pores. Total porosity and surface area increased with nHA content due to the improved fiber stability following deposition of material ink. Consequently, degradation rate and bioactivity increased, while compressive properties decreased. While nanorod HA particles had a more significant impact on the mechanical strength than plate-like morphology, the latter showed less crystalline order, which makes them more bioactive than nanorod HA. It is therefore important to note that the nHA microstructure broadly affects the printability of printing ink and should be considered according to the intended biomedical applications.

An in vitro and in vivo study of electrospun polyvinyl alcohol/chitosan/sildenafil citrate mat on 3D-printed polycaprolactone membrane as a double layer wound dressing.

Double-layer dermal substitutes (DS) generally provide more effective therapeutic outcomes than single-layer substitutes. The architectural design of DS incorporates an outer layer to protect against bacterial invasions and maintain wound hydration, thereby reducing the risk of infection and the frequency of dressing changes. Moreover, the outer layer is a mechanical support for the wound, preventing undue tension in the affected area. A 3D-printed polycaprolactone (PCL) membrane was utilized as the outer layer to fabricate DS wound dressing. Simultaneously, a polyvinyl alcohol/chitosan/sildenafil citrate (PVA/CS/SC) scaffold was electrospun onto the PCL membrane to facilitate cellular adhesion and proliferation. Scanning electron microscopy (SEM) analysis of the PCL filaments revealed a consistent cross-sectional surface and structure, with an average diameter of 562.72 ±â€¯29.15 µm. SEM results also demonstrated uniform morphology and beadless structure for the PVA/CS/SC scaffold, with an average fiber diameter of 366.77 ±â€¯1.81 nm for PVA/CS. The addition of SC led to an increase in fiber diameter while resulting in a reduction in tensile strength. However, drug release analysis indicated that the SC release from the sample can last up to 72 h. Animal experimentation confirmed that DS wound dressing positively accelerated wound closure and collagen deposition in the Wistar rat skin wound model.

Precision in cancer diagnostics: ultra-sensitive detection of MCF-7 breast cancer cells by gold nanostructure-enhanced electrochemical biosensing.

Timely identification of cancers is pivotal in optimizing treatment efficacy and reducing their widespread impact. This study introduces a novel biosensor for the sensitive electrochemical detection of cancer cells overexpressing mucin 1 (MUC1), a well-established model for breast cancer. The sensor substrate comprises gold columnar nanostructures obtained through glancing angle deposition (GLAD) of copper nanostructures, subsequently replaced by gold via a facile galvanic replacement process. Functionalizing these gold nanostructures with aptamers targeting the MUC1 glycoproteins, a prominent cancer biomarker, enables specific recognition of MCF-7 breast cancer cells. The proposed electrochemical sensing platform offers several advantages, including high selectivity, a wide linear range of detection, a low detection limit of 30 cells per mL, and long-term stability, rendering this sensor highly desirable for definitive breast cancer diagnosis.

Smart co-delivery of plasmid DNA and doxorubicin using MCM-chitosan-PEG polymerization functionalized with MUC-1 aptamer against breast cancer.

This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.

Smartphone-assisted lab-in-a-tube device using gold nanocluster-based aptasensor for detection of MUC1-overexpressed tumor cells.

Developing smartphone technology for point-of-care diagnosis is one of the current favorable trends in the field of biosensors. In fact, using smartphones can provide better accessibility and facility for rapid diagnosis of diseases. On the other hand, the detection of circulating tumor cells (CTCs) is one of the recent methods for the early diagnosis of cancer. Here, a new smartphone-assisted lab-in-a-tube device is introduced for the detection of Mucin 1 (MUC1) overexpressed tumor-derived cell lines using gold nanoclusters (GNCs)-based aptasensor. Accordingly, commercial polyurethane (PU) foam was first coated with graphene oxide (GO) to increase its surface area (8.45-fold), and improve its wettability. The surface of the resulting three-dimensional PU-GO (3DPU-GO) platform was then modified by MUC1 aptamer-GNCs to provide the required sensitivity and specificity through a turn "on/off" detection system. The proposed biosensor was first optimized with a spectrophotometer method. Afterward, findings were evaluated based on the red color intensity of the lab-in-a-tube system; and indicated the high ability of the biosensor for detection of MUC1-overexpressed tumor cell lines in the range of 250-20,000 cells mL-1 with a limit of detection of 221 cells mL-1. In addition, the developed biosensor showed a decent selectivity against positive-control cell lines (MCF-7, and HT-29) in comparison to negative-control cell lines (HEK293, and L929). Notably, the results represented good accordance with reference methods including spectroscopy devices. Ultimately, the results of this work bring a new perspective to the field of point-of-care detection and can be considered in future biosensors.

Effects of low-intensity pulsed ultrasound stimulation on cell seeded 3D hybrid scaffold as a novel strategy for meniscus regeneration: An in vitro study.

Menisci are fibrocartilaginous structures in the knee joint with an inadequate regenerative capacity, which causes low healing potential and further leads to osteoarthritis. Recently, three-dimensional (3D) printing techniques and ultrasound treatment have gained plenty of attention for meniscus tissue engineering. The present study investigates the effectiveness of low-intensity pulsed ultrasound stimulations (LIPUS) on the proliferation, viability, morphology, and gene expression of the chondrocytes seeded on 3D printed polyurethane scaffolds dip-coated with gellan gum, hyaluronic acid, and glucosamine. LIPUS stimulation was performed at 100, 200, and 300 mW/cm2 intensities for 20 min/day. A faster gap closure (78.08 ± 2.56%) in the migration scratch assay was observed in the 200 mW/cm2 group after 24 h. Also, inverted microscopic and scanning electron microscopic images showed no cell morphology changes during LIPUS exposure at different intensities. The 3D cultured chondrocytes under LIPUS treatment revealed a promotion in cell proliferation rate and viability as the intensity doses increased. Additionally, LIPUS could stimulate chondrocytes to overexpress the aggrecan and collagen II genes and improve their chondrogenic phenotype. This study recommends that the combination of LIPUS treatment and 3D hybrid scaffolds can be considered as a valuable treatment for meniscus regeneration based on our in vitro data.

Fabrication and characterization of novel polyhydroxybutyrate-keratin/nanohydroxyapatite electrospun fibers for bone tissue engineering applications.

The role of scaffolds in bone regeneration is of great importance. Here, the electrospun scaffolds of poly (3-hydroxybutyrate)-keratin (PHB-K)/nanohydroxyapatite (nHA) with different morphologies (long nanorods (HAR) and very short nanorods (HAP)) and weight percentages (up to 10 w/w%) of nHA were fabricated and characterized. The fibers integrity, the porosity of above 80%, and increase in pore size up to 16 µm were observed by adding nHA. The nanofibers crystallinity increased by 13.5 and 22.8% after the addition of HAR and HAP, respectively. The scaffolds contact angle decreased by almost 20° and 40° after adding 2.5 w/w% HAR and HAP, respectively. The tensile strength of the scaffolds increased from 2.99 ± 0.3 MPa for PHB-K to 6.44 ± 0.16 and 9.27 ± 0.04 MPa for the scaffolds containing 2.5 w/w% HAR and HAP, respectively. After immersing the scaffolds into simulated body fluid (SBF), the Ca concentration decreased by 55% for HAR- and 73% for HAP-containing scaffolds, showing the bioactivity of nHA-containing scaffolds. The results of cell attachment, proliferation, and viability of MG-63 cells cultured on the nanocomposites showed the positive effects of nHA. The results indicate that the nanocomposite scaffolds, especially HAP-containing ones, can be suitable for bone tissue engineering applications.

An in vitro and in vivo study of PCL/chitosan electrospun mat on polyurethane/propolis foam as a bilayer wound dressing.

In the current study, we fabricated a bilayer wound dressing consisting of an electrospun poly-ε-caprolactone/chitosan (PCL/CS) fibrous mat as the sublayer and a polyurethane (PU) foam coated with ethanolic extract of propolis (EEP) as the top layer. By blending the solutions of PCL and CS, we fabricated an electrospun mat consisting of bead-free and uniform nanofibers with enhanced hydrophilicity, swelling ratio, and degradation properties. To further enhance the mechanical and antibacterial properties, we electrospun the PCL/CS solution on a PU foam coated with EEP to fabricate the PCL/CS-PU/EEP bilayer wound dressing. Furthermore, the PCL/CS-PU/EEP bilayer wound dressing demonstrated enhanced cell compatibility and healing properties through in vitro and in vivo studies. Therefore, the PCL/CS-PU/EEP bilayer wound dressing offers great potential to be used as a wound dressing because of its suitable mechanical properties, swelling profile, antibacterial activity, biocompatibility, and wound healing properties.

Graphene oxide quantum dot-chitosan nanotheranostic platform as a pH-responsive carrier for improving curcumin uptake internalization: In vitro & in silico study.

We herein fabricated a cancer nanotheranostics platform based on Graphene Oxide Quantum Dot-Chitosan-polyethylene glycol nanoconjugate (GOQD-CS-PEG), which were targeted with MUC-1 aptamer towards breast and colon tumors. The interaction between aptamer and MUC-1 receptor on the desired cells was investigated utilizing molecular docking. The process of curcumin release was investigated, as well as the potential of the produced nanocomposite in targeted drug delivery, specific detection, and photoluminescence imaging. The fluorescence intensity of GOQD-CS-PEG was reduced due to transferred energy between (cytosine-guanin) base pairs in the hairpin structure of the aptamer, resulting in an "on/off" photoluminescence bio-sensing. Interestingly, the integration of pH-responsive chitosan nanoparticles in the nanocomposite results in a smart nanocomposite capable of delivering more curcumin to desired tumor cells. When selectively binds to the MUC-1 receptor, the two strands of aptamer separate in acidic conditions, resulting in a sustained drug release and photoluminescence recovery. The cytotoxicity results also revealed that the nanocomposite was more toxic to MUC-1-overexpressed tumor cells than to negative control cell lines, confirming its selective targeting. As a result, the proposed nanocomposite could be used as an intelligent cancer nanotheranostic platform for tracing MUC-1-overexpressed tumor cells and targeting them with great efficiency and selectivity.

Fabrication and assessment of a novel hybrid scaffold consisted of polyurethane-gellan gum-hyaluronic acid-glucosamine for meniscus tissue engineering.

The meniscus has inadequate intrinsic regenerative capacity and its damage can lead to degeneration of articular cartilage. Meniscus tissue engineering aims to restore an injured meniscus followed by returning its normal function through bioengineered scaffolds. In the present study, the structural and biological properties of 3D-printed polyurethane (PU) scaffolds dip-coated with gellan gum (GG), hyaluronic acid (HA), and glucosamine (GA) were investigated. The optimum concentration of GG was 3% (w/v) with maintaining porosity at 88.1%. The surface coating of GG-HA-GA onto the PU scaffolds increased the compression modulus from 30.30 kPa to 59.10 kPa, the water uptake ratio from 27.33% to 60.80%, degradation rate from 5.18% to 8.84%, whereas the contact angle was reduced from 104.8° to 59.3°. MTT assay, acridine orange/ethidium bromide (AO/EB) fluorescent staining, and SEM were adopted to assess the behavior of the seeded chondrocytes on scaffolds, and it was found that the ternary surface coating stimulated the cell proliferation, viability, and adhesion. Moreover, the coated scaffolds showed higher expression levels of collagen II and aggrecan genes at day 7 compared to the control groups. Therefore, the fabricated PU-3% (w/v) GG-HA-GA scaffold can be considered as a promising scaffold for meniscus tissue engineering.

A 3D macroporous and magnetic Mg2SiO4-CuFe2O4 scaffold for bone tissue regeneration: Surface modification, in vitro and in vivo studies.

Macroporous scaffolds with bioactivity and magnetic properties can be a good candidate for bone regeneration and hyperthermia. In addition, modifying the surface of the scaffolds with biocompatible materials can increase their potential for in vivo applications. Here, we developed a multifunctional nanocomposite Mg2SiO4-CuFe2O4 scaffold for bone regeneration and hyperthermia. The surface of scaffold was coated with various concentrations of poly-3-hydroxybutyrate (P3HB, 1-5% (w/v)). It was observed that 3% (w/v) of P3HB provided a favorable combination of porosity (79 ± 2.1%) and compressive strength (3.2 ± 0.11 MPa). The hyperthermia potential of samples was assessed in the presence of various magnetic fields in vitro. The coated scaffolds showed a lower degradation rate than the un-coated one up to 35 days of soaking in simulated biological medium. Due to the porous and specific morphology of P3HB, it was found that in vitro bioactivity and cell attachment were increased on the scaffold. Moreover, it was observed that the P3HB coating improved the cell viability, alkaline phosphatase activity, and mineralization of the scaffold. Finally, we studied the bone formation ability of the scaffolds in vivo, and implanted the developed scaffold in the rat's femur for 8 weeks. Micro-computed tomography results including bone volume fraction and trabecular thickness exhibited an improvement in the bone regeneration of the coated scaffold compared to the control. The overall results of this study introduce a highly macroporous scaffold with multifunctional performance, noticeable ability in bone regeneration, and hyperthermia properties for osteosarcoma.

Promoting keratocyte stem like cell proliferation and differentiation by aligned polycaprolactone-silk fibroin fibers containing Aloe vera.

There is a long history behind applying biological macromolecules like Aloe vera (AV) in regenerative medicine; endowed with anti-inflammatory and antimicrobial activities besides improving immune activity, AV has always been of particular interest to regenerate/reconstruct injuries and burns. In the present study, aligned electrospun polycaprolactone (PCL)-silk fibroin (SF) fibers containing different percentages of AV (0, 2.5, 5, and 7.5%wt) were fabricated for stromal regeneration. The results illustrated that a uniform bead-free structure was obtained, and the AV incorporation decreased the mean fiber diameter from 552 down to 182 nm and led to more alignment in the fibers. The Young's modulus raised from 4.96 to 5.26 MPa by higher amount of AV up to 5%wt. It is noteworthy that both the fiber alignment and AV affected the scaffolds' transparency and water uptake to increase. The human stromal keratocyte cells (hSKC)s culture revealed that the addition of AV and morphological properties of scaffolds encouraged cell adhesion and proliferation. The mRNA expression level for keratocan and ALDH3A1 and immunocytochemistry F-actin revealed the positive effect of AV on hSKCs differentiation. Our study indicated the promising potential of AV as a biological macromolecule for stromal tissue regeneration.

In Vitro Study of the Recruitment and Expansion of Mesenchymal Stem Cells at the Interface of a Cu-Doped PCL-Bioglass Scaffold.

Developing new barrier membranes with improved biomechanical characteristics has acquired much interest owing to their crucial role in the field of periodontal tissue regeneration. In this regard, we enriched the electrospun polycaprolactone (PCL)/gelatin (Gel) membranes by adding bioglass (BG) or Cu-doped bioglass (CuBG) and examined their cellular adhesion and proliferation potential in the presence of alveolar bone marrow-derived mesenchymal stem cells (aBMSCs). The membranes were fabricated and characterized using mechanical strength, SEM, FTIR, EDX, and ICP assay. Besides, aBMSCs were isolated, characterized, and seeded with a density of 35,000 cells in each experimental group. Next, the cellular morphology, cell adhesion capacity, proliferation rate, and membrane antibacterial activity were assessed. The results displayed a significant improvement in the wettability, pore size, and Young's modulus of the PCL membrane following the incorporation of gelatin and CuBG particles. Moreover, all scaffolds exhibited reasonable biocompatibility and bioactivity in physiological conditions. Although the PCL/Gel/CuBG membrane revealed the lowest primary cell attachment, cells were grown properly and reached the confluent state after seven days. In conclusion, we found a reasonable level of attachment and proliferation of aBMSCs on all modified membranes. Meanwhile, a trace amount of Cu provided superiority for PCL/Gel/CuBG in periodontal tissue regeneration.

Mesoporous silica@chitosan@gold nanoparticles as "on/off" optical biosensor and pH-sensitive theranostic platform against cancer.

A cancer nanotheranostic system was fabricated based on mesoporous silica@chitosan@gold (MCM@CS@Au) nanosystem targeted by aptamer toward the MUC-1 positive tumor cells. Subsequently, curcumin as an efficient herbal anticancer drug was first encapsulated into chitosan-triphosphate nanoparticles and then the resulted nanoparticle was loaded into the nanosystem (MCM@CS@Au-Apt). The nanosystem successful fabrication was approved at each synthesis step through FTIR, XRD, BET, DLS, FE-SEM, HRTEM, and fluorescence spectroscopy. Besides, the interaction between aptamer and curcumin was evaluated using full atomistic molecular dynamics simulations. The mechanism of curcumin release was likewise investigated through different kinetic models. Afterwards, the potential of the designed nanosystem in targeted imaging, and drug delivery was evaluated using fluorescence microscopy and flow cytometry. It was found that the energy transfer between the base pairs in the hairpin of double strands of DNA aptamer acts as a quencher for MCM@CS@Au fluorescence culminating in an "on/off" optical biosensor. On the other hand, the presence of pH-sensitive chitosan nanoparticles creates smart nanosystem to deliver more curcumin into the desired cells. Indeed, when the aptamer specifically binds to the MUC-1 receptor, its double strands separate under the low pH condition, leading to the drug release and the recovery of the fluorescence ("On" state). Based on the toxicity results, this nanosystem had more toxicity toward the MUC-1-positive tumor cells than MUC-1-negative cells, representing its selective targeting. Therefore, this nanosystem could be introduced as a smart anticancer nanotheranostic system for tracing particular biomarkers (MUC-1), non-invasive fluorescence imaging, and targeted curcumin delivery.

Bioprinted Membranes for Corneal Tissue Engineering: A Review.

Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients still face several issues due to a lack of healthy donor corneas, and rejection is another unknown risk of corneal transplant tissue. Corneal tissue engineering (CTE) has gained significant consideration as an efficient approach to developing tissue-engineered scaffolds for corneal healing and regeneration. Several approaches are tested to develop a substrate with equal transmittance and mechanical properties to improve the regeneration of cornea tissue. In this regard, bioprinted scaffolds have recently received sufficient attention in simulating corneal structure, owing to their spectacular spatial control which produces a three-cell-loaded-dimensional corneal structure. In this review, the anatomy and function of different layers of corneal tissue are highlighted, and then the potential of the 3D bioprinting technique for promoting corneal regeneration is also discussed.