Integrating substrateless electrospinning with textile technology for creating biodegradable three-dimensional structures
Abstract

The present study describes a unique way of integrating substrateless electrospinning process with textile technology. We developed a new collector design that provided a pressure-driven, localized cotton-wool structure in free space from which continuous high strength yarns were drawn. An advantage of this integration was that the textile could be drug/dye loaded and be developed into a core–sheath architecture with greater functionality. This method could produce potential nanotextiles for various biomedical applications.

John Joseph Article
Electrospun polymeric core–sheath yarns as drug eluting surgical sutures
Abstract

Drug-coated sutures are widely used as delivery depots for antibiotics and anti-inflammatory drugs at surgical wound sites. Although drug-laden coating provides good localized drug concentration, variable loading efficiency and release kinetics limits its use. Alternatively, drug incorporation within suture matrices is hampered by the harsh fabrication conditions required for suture-strength enhancement. To circumvent these limitations, we fabricated mechanically robust electrospun core–sheath yarns as sutures, with a central poly-l-lactic acid core, and a drug-eluting poly-lactic-co-glycolic acid sheath. The electrospun sheath was incorporated with aceclofenac or insulin to demonstrate versatility of the suture in loading both chemical and biological class of drugs. Aceclofenac and insulin incorporated sutures exhibited 15% and 4% loading, and release for 10 and 7 days, respectively. Aceclofenac sutures …

John Joseph Article
Effect of embedded plasmonic Au nanoparticles on photocatalysis of electrospun TiO2 nanofibers
Abstract

The present study demonstrates an original approach by which Au nanoparticles (∼10 nm) are embedded into TiO2 fibers via electrospinning. The photocatalytic performance of the resultant fibrous material was studied and related to the architecture and the nature of the internal interfaces in the composite. It was found that embedment of nano Au particles into the TiO2 fiber significantly improved the photocatalytic performance as compared to non-embedded ones. Electrospun fibers with the Au nanoparticles (∼10 nm) showed an average fiber diameter of ∼380 nm. The photocatalytic studies of Au embedded TiO2 fibers using ultra-violet (UV) visible spectroscopy showed ∼35% increase in photocatalytic activity when compared to the TiO2 fibers without the Au nanoparticles after 7 hrs of UV irradiation. This increase in photocatalysis was attributed to the ability of Au to increase charge separation in TiO2 and also

John Joseph Article
Electrospun yarn reinforced nanoHA composite matrix as a potential bone substitute for enhanced regeneration of segmental defects
Abstract

Nanohydroxyapatite (nanoHA) is a well-established synthetic bone substitute with excellent osteoconduction and osteointegration. However, brittleness coupled with slow degradation curtails its load-bearing and bone regeneration potential, respectively. To address these limitations, nanoHA composite matrix reinforced with electrospun fibrous yarns was fabricated and tested in vitro and in vivo. Different weight percentages (5, 10, 15 wt%) and varying lengths (short and continuous) of poly(l-lactic acid) yarns were randomly dispersed in a gelatinous matrix containing nanoHA. This significantly improved the compressive strength as well as work of fracture, especially for continuous yarns at high weight percentages (10 and 15 wt%). Incorporation of yarns did not adversely affect the pore size (50–350 μm) or porosity of the scaffolds as well as the in vitro cellular response. Finally, when tested in a critical-sized …

John Joseph Article
Stable titania nanostructures on stainless steel coronary stent surface for enhanced corrosion resistance and endothelialization
Abstract

Stainless steel (SS) coronary stents continue to present risk of in‐stent restenosis that impact its long term safety and efficacy. The present work focuses on developing a drug‐free and polymer‐less surface on coronary stents by utilizing a titania (TiO2) nanotexturing approach through hydrothermal processing, that will offer improved stent performance in vivo. Mechanically stable and durable nanotextured coatings are obtained on SS stents that also offer good corrosion resistance. In vitro vascular cell (endothelial and smooth muscle cells) studies on surface modified SS show preferential rapid endothelialization with enhanced nitric oxide production and reduce smooth muscle cell proliferation, in comparison to unmodified SS. In vivo evaluation of the nanotextured stents after subcutaneous implantation in rabbits show reduced irritability and minimal localized inflammatory response. These beneficial effects …

John Joseph Article
Transforming nanofibers into woven nanotextiles for vascular application
Abstract

This study investigates the unique properties, fabrication technique, and vascular applications of woven nanotextiles made from low-strength nanoyarns, which are bundles of thousands of nanofibers. An innovative robotic system was developed to meticulously interweave nanoyarns in longitudinal and transverse directions, resulting in a flexible, but strong woven product. This is the only technique for producing seamless nanotextiles in tubular form from nanofibers. The porosity and the mechanical properties of nanotextiles could be substantially tuned by altering the number of nanoyarns per unit area. Investigations of the physical and biological properties of the woven nanotextile revealed remarkable and fundamental differences from its nonwoven nanofibrous form and conventional textiles. This enhancement in the material property was attributed to the multitude of hierarchically arranged nanofibers in the …

John Joseph Article
Stanene‐Based Nanosheets for β‐Elemene Delivery and Ultrasound‐Mediated Combination Cancer Therapy
Abstract

Ultrasound (US)‐mediated sonodynamic therapy (SDT) has emerged as a superior modality for cancer treatment owing to the non‐invasiveness and high tissue‐penetrating depth. However, developing biocompatible nanomaterial‐based sonosensitizers with efficient SDT capability remains challenging. Here, we employed a liquid‐phase exfoliation strategy to obtain a new type of two‐dimensional (2D) stanene‐based nanosheets (SnNSs) with a band gap of 2.3 eV, which is narrower than those of the most extensively studied nano‐sonosensitizers, allowing a more efficient US‐triggered separation of electron (e−)‐hole (h+) pairs for reactive oxygen species (ROS) generation. In addition, we discovered that such SnNSs could also serve as robust near‐infrared (NIR)‐mediated photothermal therapy (PTT) agents owing to their efficient photothermal conversion, and serve as nanocarriers for anticancer drug …

John Joseph Article
TiO 2 nanoparticles@ TiO 2 nanofibers–an innovative one-dimensional material for dye-sensitized solar cells
Abstract

We report a unique one-dimensional (1-D) morphology of TiO2 having TiO2 nanoparticles decorating the surface of TiO2 nanofibers fabricated by a simultaneous electrospinning and electrospraying technique. The composite made by both nanofibers and nanoparticles is used as a photoanode material for dye-sensitized solar cells (DSCs) which helped in overcoming the limitations associated with nanofibers and nanoparticles when employed separately. The DSC showed an excellent efficiency of 7.89% (for a square-shaped cell of area 0.2 cm2) in comparison to 6.87% for the nanoparticulate DSC and 5.21% for the nanofiber DSC (for cells of the same area and thickness) which is an impressive value when literature on DSC fabrication with 1-D nanostructures for DSCs is concerned.

John Joseph Article
BBB pathophysiology–independent delivery of siRNA in traumatic brain injury
Abstract

Small interfering RNA (siRNA)–based therapeutics can mitigate the long-term sequelae of traumatic brain injury (TBI) but suffer from poor permeability across the blood-brain barrier (BBB). One approach to overcoming this challenge involves treatment administration while BBB is transiently breached after injury. However, it offers a limited window for therapeutic intervention and is applicable to only a subset of injuries with substantially breached BBB. We report a nanoparticle platform for BBB pathophysiology–independent delivery of siRNA in TBI. We achieved this by combined modulation of surface chemistry and coating density on nanoparticles, which maximized their active transport across BBB. Engineered nanoparticles injected within or outside the window of breached BBB in TBI mice showed threefold higher brain accumulation compared to nonengineered PEGylated nanoparticles and 50% gene silencing …

John Joseph Article
Successful reduction of neointimal hyperplasia on stainless steel coronary stents by titania nanotexturing
Abstract

Bare metal stents (BMSs) of stainless steel (SS) were surface engineered to develop nanoscale titania topography using a combination of physical vapor deposition and thermochemical processing. The nanoleafy architecture formed on the stent surface remained stable and adherent upon repeated crimping and expansion, as well as under flow. This titania nanoengineered stent showed a preferential proliferation of endothelial cells over smooth muscle cells in vitro, which is an essential requirement for improving the in vivo endothelialization, with concurrent reduction of intimal hyperplasia. The efficacy of this surface-modified stent was assessed after implantation in rabbit iliac arteries for 8 weeks. Significant reduction in neointimal thickening and thereby in-stent restenosis with complete endothelial coverage was observed for the nanotextured stents, compared to BMSs, even without the use of any …

John Joseph Article
Simultaneous targeting of primary tumor, draining lymph node, and distant metastases through high endothelial venule-targeted delivery
Abstract

Cancer patients with malignant involvement of tumor-draining lymph nodes (TDLNs) and distant metastases have the poorest prognosis. A drug delivery platform that targets the primary tumor, TDLNs, and metastatic niches simultaneously, remains to be developed. Here, we generated a novel monoclonal antibody (MHA112) against peripheral node addressin (PNAd), a family of glycoproteins expressed on high endothelial venules (HEVs), which are present constitutively in the lymph nodes (LNs) and formed ectopically in the tumor stroma. MHA112 was endocytosed by PNAd-expressing cells, where it passed through the lysosomes. MHA112 conjugated antineoplastic drug Paclitaxel (Taxol) (MHA112-Taxol) delivered Taxol effectively to the HEV-containing tumors, TDLNs, and metastatic lesions. MHA112-Taxol treatment significantly reduced primary tumor size as well as metastatic lesions in a number of mouse …

John Joseph Article
Cabozantinib unlocks efficient in vivo targeted delivery of neutrophil-loaded nanoparticles into murine prostate tumors
Abstract

A major barrier to the successful application of nanotechnology for cancer treatment is the suboptimal delivery of therapeutic payloads to metastatic tumor deposits. We previously discovered that cabozantinib, a tyrosine kinase inhibitor, triggers neutrophil-mediated anticancer innate immunity, resulting in tumor regression in an aggressive PTEN/p53-deficient genetically engineered murine model of advanced prostate cancer. Here, we specifically investigated the potential of cabozantinib-induced neutrophil activation and recruitment to enhance delivery of BSA-coated polymeric nanoparticles (BSA-NPs) into murine PTEN/p53-deficient prostate tumors. On the basis of the observation that BSA coating of NPs enhanced association and internalization by activated neutrophils by approximately 6-fold in vitro, relative to uncoated NPs, we systemically injected BSA-coated, dye-loaded NPs into prostate-specific PTEN/p53 …

John Joseph Article
Overcoming barriers for intra-articular delivery of disease-modifying osteoarthritis drugs
Abstract

Despite four decades of research in intra-articular drug delivery systems (DDS) and two decades of advances in disease-modifying osteoarthritis drugs (DMOADs), there is still no clinically available disease-modifying therapy for osteoarthritis (OA). Multiple barriers compromise intra-articular DMOAD delivery. Although multiple exciting approaches have been developed to overcome these barriers, there are still outstanding questions. We make several recommendations that can help in fully overcoming these barriers. Considering OA heterogeneity, we also propose a patient-centered, bottom-up workflow to guide preclinical development of DDS-based intra-articular DMOAD therapies. Overall, we expect this review to inspire paradigm-shifting innovations for developing next-generation DDS that can enable clinical translation of intra-articular DMOADs.

John Joseph Article
Electrospinning apparatus and method for producing multi-dimensional structures and core-sheath yarns
Abstract

Electrospinning apparatus and method for producing multi-dimensional structures such as one-dimensional continuous yarns, two-dimensional mats and three-dimensional cotton-like fluffy scaffolds is disclosed. Further, electrospinning apparatus and method with single collector geometry for producing multi-dimensional structures and core-sheath yarns are disclosed.

John Joseph Article
Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens
Abstract

Although parental vaccines offer long-term protection against homologous strains, they rely exclusively on adaptive immune memory to produce neutralizing antibodies that are ineffective against emerging viral variants. Growing evidence highlights the multifaceted functions of trained immunity to elicit a rapid and enhanced innate response against unrelated stimuli or pathogens to subsequent triggers. This review discusses the protective role of trained immunity against respiratory pathogens and the experimental models essential for evaluating novel inducers of trained immunity. The review further elaborates on the potential of trained immunity to leverage protection against pathogens via the molecular patterns of antigens by pathogen recognition receptors (PPRs) on innate immune cells. The review also focuses on integrating trained innate memory with adaptive memory to shape next-generation vaccines by coupling each one’s unique characteristics.

John Joseph Article
Strong, flexible, and thrombus-free woven nanotextile based vascular grafts, and method of production thereof
Abstract

The present invention relates to woven tubular nanotextiles, fabrication thereof using a weaving apparatus, and use thereof in vascular graft applications. The woven nanotextile conduit is 0.1 to 50 mm in diameter and includes a multitude of hierarchically arranged nanofibers. They are made from low strength bundled nanoyarns containing thousands of nanofibers with improved mechanical strength. The weaving apparatus interweaves the warp and weft yarns in longitu dinal and transverse directions, resulting in a flexible and strong woven product. The physical and biological proper ties of the woven nanotextile were significantly enhanced when compared to non-woven nanofibrous form and con ventional medical textiles. The nanotextile displayed super hydrophilic behavior in an otherwise hydrophobic material and when implanted as a vascular graft was robust, sutur able, kink-proof and non-thrombogenic …

John Joseph Article
Effective decellularisation of human saphenous veins for biocompatible arterial tissue engineering applications: Bench optimisation and feasibility in vivo testing
Abstract

Human saphenous vein (hSV) and synthetic grafts are commonly used conduits in vascular grafting, despite high failure rates. Decellularising hSVs (D-hSVs) to produce vascular scaffolds might be an effective alternative. We assessed the effectiveness of a detergent-based method using 0% to 1% sodium dodecyl sulphate (SDS) to decellularise hSV. Decellularisation effectiveness was measured in vitro by nuclear counting, DNA content, residual cell viability, extracellular matrix integrity and mechanical strength. Cytotoxicity was assessed on human and porcine cells. The most effective SDS concentration was used to prepare D-hSV grafts that underwent preliminary in vivo testing using a porcine carotid artery replacement model. Effective decellularisation was achieved with 0.01% SDS, and D-hSVs were biocompatible after seeding. In vivo xeno-transplantation confirmed excellent mechanical strength and …

John Joseph Article
Electrospinning apparatus and method for producing multi-dimensional structures and core-sheath yarns
Abstract

Electrospinning apparatus and method for producing multi-dimensional structures such as one-dimensional continuous yarns, two-dimensional mats and three-dimensional cotton-like fluffy scaffolds is disclosed. Further, electrospinning apparatus and method with single collector geometry for producing multi-dimensional structures and core-sheath yarns are disclosed.

John Joseph Article