Silk Fibroin and Its Nanocomposites for Wound Care: A Comprehensive Review.

For most individuals, wound healing is a highly organized, straightforward process, wherein the body transitions through different phases in a timely manner. However, there are instances where external intervention becomes necessary to support and facilitate different phases of the body's innate healing mechanism. Furthermore, in developing countries, the cost of the intervention significantly impacts access to treatment options as affordability becomes a determining factor. This is particularly true in cases of long-term wound treatment and management, such as chronic wounds and infections. Silk fibroin (SF) and its nanocomposites have emerged as promising biomaterials with potent wound-healing activity. Driven by this motivation, this Review presents a critical overview of the recent advancements in different aspects of wound care using SF and SF-based nanocomposites. In this context, we explore various formats of hemostats and assess their suitability for different bleeding situations. The subsequent sections discuss the primary causes of nonhealing wounds, i.e., prolonged inflammation and infections. Herein, different treatment strategies to achieve immunomodulatory and antibacterial properties in a wound dressing were reviewed. Despite exhibiting excellent pro-healing properties, few silk-based products reach the market. This Review concludes by highlighting the bottlenecks in translating silk-based products into the market and the prospects for the future.

Photopolymerized silk fibroin gel for advanced burn wound care.

The future of burn wound treatment lies in developing bioactive dressings for faster and more effective healing and regeneration. Silk fibroin (SF) hydrogels have proven regenerative abilities and are being explored as a burn wound dressing. However, unfavorable gelation conditions limit the processability and clinical application. Herein a white light-responsive photopolymerization technique was adapted for gelation via photooxidation of tyrosine. To render the gel suitable for application to irregular and non-planar burn surfaces, SF gel-incorporated dressing (SFD) was fabricated. The mild gelation conditions using white light afforded the loading of drugs for local delivery. The moisture balance ability of the dressing was confirmed by the favorable measures of swelling capacity (106 ± 1 %) and moisture retention (≈10 h). The in vitro cytocompatibility of the gel was confirmed using HaCaT cells. Finally, in vivo performance of the SFD was tested on a second-degree burn in a rodent model. The gross analysis and histological assessment revealed scarless healing in SFD-treated groups. Overall, the SFD developed in this work is shown to be a promising candidate for advanced burn wound care.

Silk composite interfacial layer eliminates rebleeding with chitosan-based hemostats.

Chitosan foams are among the approved hemostats for pre-hospital hemorrhagic control but suffer from drawbacks related to mucoadhesiveness and rebleeding. Herein, we have developed a designer bilayered hemostatic foam consisting of a bioactive layer composed of silica particles (≈300 nm) and silk fibroin to serve as the tissue interfacing component on a chitosan foam. The foam composition was optimized based on the in vitro clotting behavior and cytocompatibility of individual components. In vivo analysis in a rat model demonstrated that the developed hemostat could achieve rapid clotting (31 ± 4 s), similar to a chitosan-based hemostat, but the former had significantly lower blood loss. Notably, removal of the bilayered hemostat prevented rebleeding, unlike the chitosan foam, which was associated with markedly higher incidences of rebleeding (50 %) and left behind material residue. Thus, the designer bilayered foam presented here is a potent inducer of blood clotting whilst affording easy removal with minimal rebleeding.

Prenatal diagnosis of vascular rings and outcome.

BACKGROUND: Vascular rings (VRs) present with varied symptoms and may result in significant morbidity before an accurate diagnosis is made. Prenatal diagnosis may be useful to plan surgery after birth. OBJECTIVES: The purpose of the study was to see the feasibility of accurate diagnosis of VR during antenatal ultrasound examination and describe their outcome. METHODS: This is a retrospective observational study between January 2014 and December 2019. Vascular rings were diagnosed on the basis of three vessel tracheal view and neck vessels arrangements on fetal echocardiogram. Postnatal evaluation by transthoracic echocardiography and computerized tomography angiogram was performed. Surgical repair was done as per standard indications. RESULTS: A total of 35 cases of fetal VRs (median gestational age: 24 weeks [range: 19-35]) were diagnosed during the study period. There were four dichorionic diamniotic twin gestation pregnancies. The right aortic arch (RAA) with anomalous left subclavian artery (ALSA) was suspected in 31 fetuses, double aortic arch (DAA) in 3, and circumflex aorta in 1. Twenty-six (74%) patients had successful deliveries. One patient had a spontaneous miscarriage, 2 underwent termination, and 6 were lost to follow-up. Postnatal assessment showed RAA with ALSA in 18, DAA in 5, circumflex aorta in 2, and no abnormality in 1. Twenty-two (86%) were operated (RAA with ALSA: 17, DAA: 4, and circumflex aorta: 1) and four were waiting for surgery. Two patients died due to prematurity-related complications. All survivors are symptom free during follow-up (median: 2.24; range: 0.2-5.6 years). CONCLUSIONS: Fetal echocardiography enables prenatal diagnosis and planning of postnatal repair of VRs.

1,6-heptadiynes based cyclopolymerization functionalized with mannose by post polymer modification for protein interaction.

Carbohydrate functionalized polymers or Glycopolymers have earned a great deal of interest in recent times for their potential biomedical applications. In the present study, a mannose containing glycopolymer was synthesized by cyclopolymerization of malonic acid derivative using second generation Hoveyda Grubbs' catalyst. Post-polymerization modification was done to install a propargyl moiety. Finally, functionalization of the propargylated polymer with 2-azidoethyl mannoside using azide-alkyne "click chemistry" furnished the target glycopolymer which was successfully characterized using NMR, FT-IR, mass spectroscopy and advanced polymer chromatography. The glycopolymer was found to self-assemble into capsule and spherical shape in water and DMSO respectively and these morphologies were observed through SEM and TEM. Upon interaction with Con A, the mannose containing glycopolymer showed an increment in aggregation induced fluorescence with increasing concentration of the lectin. In vitro cytotoxicity studies on MCF 7 cell line showed 90% cell viability up to glycopolymer concentration of 500 µg/mL.

Hetero-Trifunctional Malonate-Based Nanotheranostic System for Targeted Breast Cancer Therapy.

Designing multifunctional linkers is crucial for tricomponent theranostic targeted nanomedicine development as they are essential to enrich polymeric systems with different functional moieties. Herein, we have obtained a hetero-trifunctional linker from malonic acid and demonstrated its implication as an amphiphilic targeted nanotheranostic system (CB DX UN PG FL). We synthesized it with varying hydrophilic segment to fine-tune the hydrophobic/hydrophilic ratio to optimize its self-assembly. pH-responsive hydrazone-linked doxorubicin was conjugated to the backbone (UN PG FL) containing folate as a targeting ligand. Cobalt carbonyl complex was used for T2-weighted magnetic resonance imaging (MRI). Electron micrographs of optimized molecule CB DX UN PG(4 kDa)FL in an aqueous system have demonstrated about 50-60 nm-sized uniform micelles. The relaxivity study and the one-dimensional (1D) imaging experiments clearly revealed the effect of the nanotheranostics system on transverse relaxation (T2) of water molecules, which validated the system as a T2-weighted MRI contrast agent. The detailed in vitro biological studies validated the targeted delivery and anticancer potential of CB DX UN PG(4 kDa)FL. Combining the data on transverse relaxation, folate mediated uptake, and anticancer activity, the designed molecule will have a significant impact on the development of targeted theranostic.

Common arterial trunk with intact septum and hypoplastic right ventricle: An uncommon embryological entity.

Embryologically, the common arterial trunk (CAT) is due to the failure of septation by the major outflow cushions. This invariably leads to the presence of an associated large juxta-arterial ventricular septal defect. Overriding of the ventricular septum leads to its biventricular origin in more than 2/3rd of cases. Uncommonly, CAT may be associated with an intact ventricular septum (IVS) and univentricular origin. We describe an infant with CAT, intact IVS, hypoplastic right ventricle, and Ebstein's anomaly of the tricuspid valve who presented to us and palliated successfully. The embryological mechanisms are discussed in this report.

Iron(III) Coordinated Polymeric Nanomaterial: A Next-Generation Theranostic Agent for High-Resolution T1-Weighted Magnetic Resonance Imaging and Anticancer Drug Delivery.

Theranostic-based nanomedicine plays a crucial role in the field of cancer therapy. This is due to having the capability to combine both therapy and diagnosis together in a single system. Herein a new class of metal-ligand-based nanocarrier in a norbornene backbone has been designed as a theranostic system. Fe3+-terpyridine complex (Fe-Tpy) has been used here as T1 contrast agent for high-resolution MR imaging, and hydrazone-linked doxorubicin is used for effective pH-responsive delivery. Polyethylene glycol functionalized with a folic acid (peg folate) motif is used to make the entire polymeric system dispersible in water for longer retention and site-specific therapy. All these specialty functional groups are anchored in a single system by using the ring-opening metathesis polymerization (ROMP) technique under the norbornene backbone. Relaxivity study and 1D image experiments have shown the utility of Fe-Tpy complex as an effective T1 contrast agent. In vitro studies are performed to confirm the promising potentiality of the nanocarrier as the efficient nanotheranostic system in prostate cancer.

Selection of P-Glycoprotein Inhibitor and Formulation of Combinational Nanoformulation Containing Selected Agent Curcumin and DOX for Reversal of Resistance in K562 Cells.

PURPOSE: To select P-glycoprotein (P-gp) inhibitor from natural source for reversal of DOX resistance in K562 cells and to develop selected one in to nanoformulation in combination with DOX. METHODS: DOX resistant K562 (K562R) cells were developed and reversal of resistance by P-gp inhibitor was validated by co-treatment with verapamil. The p-gp inhibitors were evaluated for their potential to inhibit P-gp (calcein assay) and to reverse drug resistance (XTT cell viability assay). The selected agent, curcumin was formulated in to liposome along with DOX and characterized for size, zeta potential, encapsulation efficiency and release rate. Uptake, P-gp inhibition and reversal of acquired drug resistance in K562R cells were performed. RESULTS: P-gp inhibitors such as biochanin-A and curcumin were marked suitable for combination with DOX. However, only curcumin could increase the sensitivity of DOX at all dosing levels, therefore used for further studies. Liposomes loaded with curcumin were formulated and characterized where a prolonged release was observed. The uptake of liposomal curcumin was comparable to nanodispersed curcumin but had lower cytotoxicity. DOX and curcumin coloaded liposomes successfully reversed DOX resistance in K562 cells. CONCLUSION: The coloaded liposomes increased the safety of curcumin with improved efficacy thus can be employed for reversal of acquired DOX resistance.

Selection and optimization of nano-formulation of P-glycoprotein inhibitor for reversal of doxorubicin resistance in COLO205 cells.

OBJECTIVE: The prime objective of current work was to develop a strategy for preparation of combinational nano-formulation for reversal of drug resistance. METHODS: As a model system, doxorubicin (DOX)-resistant COLO205 cells were developed and validated. From co-treatment studies with DOX, curcumin was selected as it reversed DOX-resistance at lowest concentration. In an attempt to increase its solubility, curcumin was encapsulated into hydroxypropyl-ß-cyclodextrin (HP-ß-CD). Here, we propose that presence of stabilizer overcomes its low encapsulation efficiency. Thus, we evaluated curcumin encapsulation in HP-ß-CD in presence of different stabilizers and organic solvents. Finally, the effect of nanocurcumin with liposomal DOX was studied for reversal of resistance in COLO205 cells. KEY FINDINGS: In the process encapsulation, selective optimization of organic solvent by freeze-drying was found to be appropriate among other methods. From optimization studies with different organic solvent (acetone and dichloromethane) and stabilizer [polyvinyl alcohol (PVA) and Pluronics], HP-ß-CD-encapsulated curcumin prepared using acetone in PVA-stabilized dispersion increased encapsulation (60%) with size of ~40 nm. Prepared nano-curcumin reversed the DOX resistance effectively in combination with liposomal DOX. CONCLUSIONS: Curcumin reversed DOX resistance in COLO205 cells at low concentration and enhanced curcumin encapsulation in HP-ß-CD was noted in presence of PVA. Further, it was observed that prepared HP-ß-CD-encapsulated curcumin is equi-efficacious to nano-dispersed curcumin.

Transcatheter pulmonary valve perforation using chronic total occlusion wire in pulmonary atresia with intact ventricular septum.

BACKGROUND: Perforation of pulmonary valve using radiofrequency ablation in pulmonary atresia with intact ventricular septum (PA IVS) is a treatment of choice. However, significant cost of the equipment limits its utility, especially in the developing economies. OBJECTIVE: To assess the feasibility, safety, and efficacy of perforation of pulmonary valve using chronic total occlusion (CTO) wires in patients with PA IVS as an alternative to radiofrequency ablation. METHODS: This is a single-center, nonrandomized, retrospective study conducted during June 2008 to September 2015. Twenty-four patients with PA IVS were selected for the procedure during the study period. The median age and weight of the study population were 8. days and 2.65 kg, respectively. Four patients were excluded after right ventricular angiogram as they showed right ventricular-dependent coronary circulation. The pulmonary valve perforation was attempted using various types of CTO wires based on the tip load with variable penetrating characteristics. RESULTS: The procedure was successful in 16 of twenty patients using CTO wires: Shinobi in nine, Miracle in four, CROSS-IT in two, and Conquest Pro in one. Two patients had perforation of right ventricular outflow tract (RVOT). Pericardiocentesis was required in one patient to relieve cardiac tamponade. Later, the same patient underwent successful hybrid pulmonary valvotomy. The other patient underwent ductus arteriosus (DA) stenting. Balloon atrial septostomy was needed in three cases with systemic venous congestion. Desaturation was persistent in five cases necessitating DA or RVOT stenting to augment pulmonary blood flow. There were two early and two late deaths. The mean follow-up was 22.66 ± 16 months. Three patients underwent one and half ventricle repair and one Blalock-Taussig shunt during follow-up. CONCLUSION: Perforation of the pulmonary valve can be done successfully using CTO wires in selected cases of pulmonary atresia with intact ventricular septum.

Formulation and Optimization of Doxorubicin and Biochanin A Combinational Liposomes for Reversal of Chemoresistance.

Circumvention of drug resistance still remains a challenge in the development of anticancer therapeutics. Combinational nano-formulations provide many avenues for effective cancer therapy and reversal of drug resistance. In the current study, combination of biochanin A (BioA) and doxorubicin (DOX) in liposomes were prepared and studied for its potential to reverse DOX resistance in COLO205 cells. After development and validation of DOX resistant cells of COLO205 (ColoR), dosing ratio of DOX and BioA for reversal of DOX resistance was determined by co-treatment in ColoR cells. As limited solubility and analytical data available for BioA, therefore solubility was studied for BioA and analytical method was developed for the combination. Combinational liposomes were prepared and optimized for both lipid content and surface charge by evaluating size, polydispersity index, zeta potential, and encapsulation efficiency. The optimized formulation had a size about 125 nm; zeta potential of -19.5 mV and 70% encapsulation efficiency (EE) for BioA. Thus, prepared combinational liposomes of DOX and BioA were evaluated for its cellular uptake and efficacy to reverse DOX resistance. From the study, increased DOX uptake and promising effect for reversal of DOX resistance was observed.

Comparative Study of Different Nano-Formulations of Curcumin for Reversal of Doxorubicin Resistance in K562R Cells.

PURPOSE: Curcumin is very well established as a chemo-therapeutic, chemo-preventive and chemo-sensitizing agent in diverse disease conditions. As the isolated pure form has poor solubility and pharmacokinetic problems, therefore it is encapsulated in to several nano-formulations to improve its bioavailability. Here in the current study, we aim to compare different nano-formulations of curcumin for their chemo-sensitizing activity in doxorubicin (DOX) resistant K562 cells. METHODS: Four different curcumin formulations were prepared namely DMSO assisted curcumin nano-dispersion (CurD, 260 nm), liposomal curcumin (CurL, 165 nm), MPEG-PCL micellar curcumin (CurM, 18 nm) and cyclodextrin encapsulated curcumin (CurN, 37 nm). The formulations were subjected to particle characterizations (size, zeta potential, release studies), followed by biological assays such as cellular uptake, P-gp inhibitory activity and reversal of DOX resistance by co-treatment with DOX. RESULTS: Curcumin uptake in K562N and K562R cells was mildly reduced when treated with CurL and CurM, while for CurD and CurN the uptake remained equivalent. However, CurL retained P-gp inhibitory activity of curcumin and with a considerable chemo-sensitizing effect but CurM showed no P-gp inhibitory activity. CurN retained above biological activities, but requires a secondary carrier under in vivo conditions. CONCLUSIONS: From the results, CurM was found to be most suitable for solubilization of curcumin where as CurL can be considered as most suitable nano-formulation for reversal of DOX resistance.

Tuning the work function of randomly oriented ZnO nanostructures by capping with faceted Au nanostructure and oxygen defects: enhanced field emission experiments and DFT studies.

The lowering of the work function (Φ) can lead to a better field emission (FE) behavior at lower threshold fields. We report on enhanced FE from randomly oriented and faceted Au-capped ZnO hetero-nanostructures (HNs) having more oxygen defects. Large-area arrays of non-aligned, faceted Au-capped ZnO HNs, such as nanowires (NWs) and triangular nanoflakes (TNFs) are grown using the chemical vapor deposition (CVD) method. Enhanced FE properties from the TNF sample resulted in a turn-on field as low as 0.52 V µm(-1) at a current density of 0.1 mA cm(-2) and a field enhancement factor (ß) as high as ≈5.16 × 10(5). Under similar experimental conditions, drawing the same current density from an NW specimen needs a higher turn-on field (0.86 V µm(-1)) and to exhibit nearly four times less field enhancement factor compared to the TNFs samples. X-ray photoelectron spectroscopy (XPS) and photoluminescence (PL) measurements confirm the presence of more oxygen defects in the TNF samples compared to the NW samples. Kelvin probe force microscopy (KPFM) measurements show the average local work function to be 4.70 ± 0.1 eV for the TNF sample, which is ≈ 0.34 eV lower than the NW sample. Using density functional theory (DFT) calculations, the estimated Φ values are found to be 4.98 eV for ZnO(0001), 4.17 eV for Au(001)/ZnO(0001) and 3.91 eV for Au(001)/Ovac-ZnO(0001) surfaces. The DFT results are qualitatively in agreement with our experimental results. The presence of Au nanostructures on top of O-deficient and sharp-tipped TNFs results in enhanced FE performance following their reduced tunneling barrier via pinning of effective Φ.

Diagnosis and management of aorto-left ventricular tunnel.

BACKGROUND: Aorto-left ventricular tunnel (ALVT) is a rare congenital extracardiac channel with progressive left ventricular dilatation needs early correction. MATERIALS AND METHODS: This is a report of diagnosis and management of aorto-left ventricular tunnel (ALVT) over a period of 11 years from a single institution. Seven patients (age range: 7 days-45 years) presented with heart failure. The diagnosis of ALVT was made by transthoracic echocardiogram in all cases. RESULTS: Treatment was refused by two patients who died during follow-up. Surgical closure of the tunnel was done in four cases, of which one needed Bentall procedure. Two patients had residual leak after the surgery. Transcatheter closure using Amplatzer muscular device was performed in two cases (for postoperative residual leak in one and primary procedure in the other). Significant hemolysis developed in one of them, necessitating the removal of the device and closed surgically. This child underwent aortic valve replacement two years later. All the remaining patients were doing well during the median follow-up of 30 months (range: 1.5-9 years). CONCLUSION: ALVT is a rare and potentially fatal anomaly that is ideally managed surgically. Catheter closure has a limited role.

Photocatalytic destruction of Escherichia coli in water by V2O5 /TiO2.

Vanadia modified titania (V2O5/TiO2) photo-catalysts are prepared by incipient wet impregnation method using aqueous ammonium metavanadate and anatase (Aldrich) titania. Titania with various loading concentrations of vanadia from 0 to 10 wt.% have been prepared and characterized by X-ray diffraction (XRD), Thermogravimetry (TGA), Laser Raman Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS), UV-Visible Spectrophotometry and Transmission Electron Microscopy (TEM). XRD study reveals that vanadia loading on titania does not bring any phase change of titania, however, diffuse (UV-Vis) reflectance spectra show that absorption edge of titania shifted from UV to visible region. TEM confirms that titania and vanadia modified titania have the particle size below 50 nm. XPS shows alteration of 2p3/2 peak of V(V) in the V2O5/TiO2 samples whereas no such change is noticed in pure V2O5 indicating the interaction between vanadia and titania support. Antibacterial activity of each sample has been investigated against Escherichia coli present in the water under both UV-Visible irradiation and UV alone. V2O5/TiO2 catalysts exhibit better photocatalytic effect than the unmodified titania and pure V2O5. It is observed that with increasing loading concentrations of V2O5 from 0 to 10 wt.% on titania support, the photocatalytic annihilation of E.coli is also increased and found to be little higher under UV alone than the UV-Visible irradiation.

Water disinfection through photoactive modified titania.

TiO(2), N-TiO(2) and S-TiO(2) samples have been prepared by various chemical methods. These samples were characterized by X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), Laser Raman spectrometer, UV-Visible spectrophotometer, field emission scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). X-ray powder diffraction study reveals that all three samples are single anatase phase of titania and the crystallinity of titania decreases with sulphur doping whereas nitrogen doping does not affect it. UV-Visible (diffuse) reflectance spectra shows that doping of titania with nitrogen and sulphur shift the absorption edge of titania from ultraviolet to visible region. XPS study confirms that both nitrogen and sulphur are well doped in the titania lattice. It is observed that nitrogen occupies at both substitutional and interstitial position in the lattice of titania. FE-SEM and TEM studies demonstrate that the particles are below 50nm range. It is found that S and N doping of titania increased its water disinfection property in the order TiO(2)

Nanoformulations for delivery of biomolecules: focus on liposomal variants for siRNA delivery.

The potency of biomolecules assures therapy for as well as prevention of many disorders. However, their stability and delivery to the site of action remain a major challenge for successful therapeutic application. With advantages of nanoformulations, such as systemic environmental protection, controlled and site specific release, many of these bio-molecules have found their place in preventive, curative, or immunization-based therapies. Nanoformulations have indeed become a boon for the delivery of biomolecules with such challenges. Among biomolecules, small interfering RNA (siRNA)-based therapeutics has broad range of applications for disorders that may be pathological, metabolic, or physiological. However, certain challenges with respect to biological and delivery constraints need a priori consideration. From this perspective, liposomal delivery has made substantial progress to meet most of the delivery-related (pharmacokinetic) problems associated with siRNA. Furthermore, need-based development has led to the evolution of variants of liposomes. In this review we focus on the scope of siRNA and the trend of rationalized development of liposomal variants to explore its potential therapeutic implication.

Polymeric modification and its implication in drug delivery: poly-ε-caprolactone (PCL) as a model polymer.

Biodegradable polymers provided the opportunity to explore beyond conventional drug delivery and turned out to be the focus of current drug delivery. In spite of availability of diverse class of polymers, several of these polymers lack important physicochemical and biological properties, limiting their widespread application in pharmaceutical drug delivery. However, most polymers in the form of blends, copolymers and functionally modified polymers have exhibited their applicability to overcome specific limitations and to produce novel and/or functionalized formulations for drug delivery as well as tissue engineering. This review aims to provide the need of polymeric modification, approaches adopted to modify and their scope. Special emphasis has been given to synthetic polyester PCL, as it is widely demonstrated in its modified form to overcome its problem of hydrophobicity and much slower degradation over the past decade. Past studies show a significantly higher utility of modified form of PCL in comparison to its native form. From the statistical analysis of these modifications and the formulations prepared, we present a basic understanding of the impact of selective modifications on the formulation design. In conclusion, we remark that a thorough understanding of the polymer and its modification has a huge potential to be the future trend for drug delivery and tissue engineering applications.