Despite notable progress, 3D-bioprinted constructs exhibit limited mechanical robustness and lack the essential ECM-mimicking features crucial for promoting bioactivity, cell growth, and tissue formation. To address these shortcomings, we devised an innovative technique that reinforces bioprinted constructs with polymeric nanofibrous yarns composed of thousands of nanofibers. Utilizing an in situ printing process, a continuous strand of nanofibrous yarn was embedded within the core of the extruded bioink to fabricate a 3D-printed construct. We optimized the key design parameters of the nanofibrous yarn, bioink, and the printing process, which are necessary for direct bioprinting of a nanofibrous yarn-reinforced 3D construct, which has never been demonstrated before. The hydrophilicity of the nanofibrous yarns promoted interfacial interaction with the bioink, while the shear stress developed at the nozzle during extrusion allowed the nanofibrous yarns to be spooled out as a single continuous strand integrated with the bioink. The micron-sized channels within the bundled nanofibrous yarn facilitated cell wicking into the nanifibrous yarn. This approach has enhanced the ability to manufacture cell-laden structures, whereby live cells are freely incorporated into a highly organized nanofibrous architecture. The resulting construct offers the high bioactivity needed for cell regeneration and the superior structural integrity required for diverse biomedical and regenerative medicine applications.

Mandibular continuity defects following tumor resection or trauma present significant reconstructive challenges, particularly for subsequent dental rehabilitation. While the fibula free flap remains the gold standard, its limited vertical height often necessitates augmentation. This prospective, single-center, non-randomized pilot clinical trial evaluated the safety and efficacy of a novel silica-coated nanohydroxyapatite-gelatin/PLLA scaffold (NANOTEX), manufactured under GMP conditions and ISO 13485-certified quality standards, for vertical augmentation over fibula flaps in ten patients undergoing segmental mandibulectomy for benign jaw tumors. Customized NANOTEX scaffolds were placed intraoperatively, and safety (inflammation, wound dehiscence, infection laboratory parameters) and efficacy (bone height gain, radiodensity, bone union, and implant stability) were assessed at baseline, 3 and 6 months. No scaffold-related serious adverse events were observed; mild to moderate inflammation and wound dehiscence were transient. Significant bone regeneration was achieved, with a mean vertical gain of 26.99% at 6 months, which was higher in regions contacting the native mandible (32.58%) compared to non-contact areas (25.02%). Radiodensity progressed from cancellous to cortical levels, and implant placement at 6 months demonstrated high stability in 88.6% of cases (ISQ > 70). Overall, NANOTEX was safe and promoted vertical bone regeneration, highlighting its translational potential for mandibular reconstruction.

Atherosclerosis is a major contributor to cardiovascular disease globally, posing significant challenges for effective management. Conventional pharmacological therapies, particularly statins and lipid-lowering agents, remain pivotal due to their accessibility and long-term benefits, but are limited by suboptimal efficacy and side-effects. Nanomedicine presents promising targeted drug delivery systems that enhance treatment specificity while reducing toxicity, and has the potential for developing personalized therapy. In interventional cardiology, advances in stent technology from bare metal stents to drug-eluting stents and bioresorbable scaffolds have improved vascular healing, however complications such as delayed endothelialization, smooth muscle cell proliferation, and thrombosis persist. To further enhance stent performance and biocompatibility, innovative surface coatings have emerged, by precisely tailoring the chemistry, topography, and biofunctionalization to optimize healing, accelerate endothelialization, and minimize restenosis/thrombosis through diverse strategies. Despite progress, challenges pertaining to coating durability, manufacturing complexity, and limited long-term clinical evidence still continue. Future research should emphasize multifunctional coatings that synergistically enhance endothelial recovery and inhibit restenosis and thrombosis, with nanotechnology and biomimicry offering significant opportunities for next-generation stent development. This review explores a spectrum of anti-atherosclerotic approaches aimed at combating cardiovascular diseases, from pharmacological agents to stents, highlighting diverse material design principles and its biological performance, recent advances in nanoengineered stent coatings, and the overall clinical landscape.

Malignant biliary obstruction presents a significant therapeutic challenge and has serious consequences including cholangitis and death. Clinically, biliary stenting using self-expanding metallic- stent(SEMS) relieves this obstruction. However, stent occlusion occurs with time due to tumor/epithelial in-growth and bacterial colonization. To achieve sustained palliative benefit of stent-based approaches, both biliary sludge formation and in-growth need to be obviated. In this study, an innovative approach was adopted to inhibit sludge deposition and tissue in-growth by developing a heparinized drug-eluting SEMS. For this, heparinisation was performed on dopamine-functionalised-stents, which averted bile protein adsorption in vitro. Further, Gemcitabine loaded polycaprolactone electrospun-nanoyarns were integrated with heparinized-SEMS to achieve sustained drug release for nearly six months in vitro. Nanoyarn integration with heparinized-SEMS did not hamper its crimping, ease of deployment or functional behaviour. In vivo safety and efficacy were evaluated for five months after implantation in porcine bile duct through Endoscopic Retrograde Cholangiopancreatography. Minimal sludge deposition with no obstruction in bile flow, good stent patency and localized-sustained drug elution were observed for nanoyarn-integrated heparinized-SEMS. No alterations in the biochemical parameters, nor any inflammatory reactions were observed in vivo, all in comparison to control-SEMS. Overall, our research established an efficient multipronged strategy to tackle malignant biliary obstruction. STATEMENT OF SIGNIFICANCE: Bile duct occlusion due to cancer has several life-threatening consequences. This is clinically treated using metallic stents, with simultaneous intravenous use of anti-cancer drugs at high-doses. Nevertheless, tumor-growth along with bile-sludge accumulation happens after stenting, causing re-occlusion. Existing research uses stent modifications that fail to tackle both simultaneously, yielding short-term efficacy. To address this, heparinized-metallic stents were modified using chemo-drug eluting polymeric-nanoyarn integration. The key features of this device are: nanoyarn-integrated, uncovered stent design facilitating easy endoscopic implantation in bile duct; reduced bile-sludge deposition; prolonged, low-dose, localised drug release that can mitigate tumor-growth; and provide long-term stent patency without stent migration. This device proved to be safe, functional and efficacious for a period of five months in pig bile duct.

Epithelial ovarian cancer is the most prevalent gynecological malignancy, characterized by high mortality rates due to its late-stage diagnosis and frequent recurrence. The current standard of care for ovarian cancer is a combination of debulking surgery followed by the conventional mode of chemotherapy. Despite significant advances in therapeutic modalities, the overall survival rate of EOC continues to be poor, mainly because low concentrations of the chemotherapeutics reach the peritoneum, which is the primary site of ovarian cancer, leading to disease relapse. Here, intraperitoneal chemotherapy gains advantage due to its ability to deliver the drug molecules directly to the peritoneal cavity and provide localized and sustained effects. This is facilitated by the use of diverse kinds of nano or micron sized delivery systems, which help in transporting drugs, vaccines, antibodies and genes appropriately to the peritoneum for its desired function. This review article delves on how intraperitoneal delivery impacts the therapy of epithelial ovarian cancer spanning the conventional therapeutic modes to the recent nanoinnovations in chemotherapy, immunotherapy and gene therapy. Graphical Illustrations: All the graphical illustrations in this article were made using bioRender.

This study exploited the water repelling hydrophobic nature of polycaprolactone (PCL) fibers for efficient filtration of water-based fluids toward development of an affordable sterile membrane filter by the process of electrospinning. Electrospun (ES) nanosized fibrous membranes of different thicknesses presented high force at break and minimal elongation supported syringe filtration. The membrane hydrophobicity facilitated easy filtration of small volumes of biological fluids (∼1 mL) without any wetting media loss. Compared to commercial filters, the developed electrospun PCL membrane filter (EPF) device exhibited excellent bacterial filtration without compromising the media quality. Electron microscopy analysis revealed bacterial entrapment onto PCL nanofibers that are in direct contact with the contaminated media. Mechanistically, an EPF with ∼0.8 mm thickness and high porosity created sinusoidal channels of different diameters that could effectively retard bacterial movement for the efficient filtration of up to 50 mL of contaminated biological media. Despite being hydrophobic, the PCL nanofiber filter had low protein binding, and its filtration quality was similar to commercial controls, assessed by cell viability assays. Thus, the EPF device can be an alternate filter sterilization platform for medical applications without compromising the filtrate's quality.

Simultaneous inhibition of multiple oncogenic signaling pathways is crucial for managing refractory cancers. This study introduces two unique core-shell nanoparticle (CS-NP) systems crafted from natural proteins that simultaneously target two crucial oncogenic pathways in refractory chronic myeloid leukemia (CML). Molecular analysis of approximately 14 refractory CML patients identified resistance to the standard treatment drug, imatinib, attributed to the overex-pression of the STAT5-transferrin pathway alongside the classic BCR-ABL fusion gene. To address this, we developed two dual-drug-loaded core-shell nanoparticles: (a) CS-NP1: Protamine sulfate nanocores carrying BCR-ABL siRNA and an albumin shell loaded with the STAT5 in-hibitor sorafenib, denoted as (PS-siRNA)-(Tf-Soraf) CS-NP; (b) CS-NP2: features a second-generation BCR-ABL inhibitor, dasatinib, in the albumin nanocore, and sorafenib in the transferrin nanoshell, labeled as (nAlb-Dasa)-(Tf-Soraf). We hypothesized that these dual-drug-loaded CS-NPs would effectively target both BCR-ABL and STAT5 pathways, with the transferrin nanoshell aiding in precise delivery to refractory CML cells overexpressing TfR1 due to STAT5 activity. Initial evaluations in drug resistant CML cell lines and patient-derived cells demonstrated significant cytotoxicity. Remarkably, even patients with BCR-ABL oncogene mutations displayed over 95% cytotoxicity with the CS-NPs. Furthermore, in vivo testing on a human xeno-graft model with a BCR-ABL+/+/STAT5+/+/TfR+/+ phenotype showcased a strong anti-tumor response. These results underscore the potential of a molecular-diagnosis-based rational design approach for protein-protein core-shell nanoparticles to simultaneously inhibit multiple oncogenic pathways, thereby overcoming resistance to targeted molecular therapies.

A modified electrospinning design was introduced to overcome the limitation in non-uniformity of the nanofibrous coating on the surface of non-conducting, statically charged polypropylene microfibers. By manipulating the charge distribution over the non-conducting surface via variations in the polarity of the Taylor cone and the electrospinning geometry, it was possible to obtain a uniformly adherent and thin nanofibrous coating over a large area to achieve a layer-by-layer simultaneous deposition of + ve and -ve fibers onto a non-conducting membrane. The uniformity and quality of this nanocoating was found to have a direct effect on particle filtration and breathability of air filters. The filter showed a high particle filtration efficiency of 96 % for 0.3 mu m particles, with excellent breathability.

The inheritable impact of exposure to graphene oxide nanoparticles (GO NPs) on vertebrate germline during critical windows of gamete development remain undetermined to date. Here, we analyzed the transgenerational effects of exposure to nano-graphene oxide particles (nGO) synthesized in house with lateral dimensions 300-600 nm and surface charge of -36.8 mV on different developmental stages of germ cells (GCs): (1) during GCs undergoing early development and differentiation, and (2) during GCs undergoing gametogenesis and maturation in adulthood. Biocompatibility analyses in Japanese medaka embryos showed lethality above 1 µg/ml and also an aberrant increase in germ cell count of both males and females at doses below the lethal dose. However, no lethality or anomalies were evident in adults up to 45 µg/ml. Long term exposure of embryos and adults for 21 days resulted in reduced fecundity. This effect was transmitted to subsequent generations, F1 and F2. Importantly, the inheritable effects of nGO in adults were pronounced at a high dose of 10 µg/ml, while 1 µg/ml showed no impact on the germline indicating lower doses used in this study to be safe. Further, expressions of selected genes that adversely affected oocyte maturation were enhanced in F1 and F2 individuals. Interestingly, the inheritance patterns differed corresponding to the stage at which the fish received the exposure.

Vocal fold (VF) scarring, a complex problem in laryngology, results from injury and inflammation of the layered architecture of the VFs. The resultant voice hoarseness, for which successful therapeutic options are currently limited, affects the patient's quality of life. A promising strategy to reverse this disorder is the use of antifibrotic drugs. The present study proposes a novel microbead-embedded injectable hydrogel that can sustain the release of the anti-fibrotic drug pirfenidone (PFD) for vocal fold scarring. Microbeads were developed using sodium alginate and gelatin, which were further embedded into a biomimetic and tissue adhesive gellan gum (GG) hydrogel. The microbead-embedded hydrogel exhibited improved injectability, viscoelasticity, tissue adhesiveness, degradability, and swelling compared to the hydrogel without beads. Additionally, the bead-embedded hydrogel could sustain the release of the PFD for a week. In vitro studies showed that the drug-loaded hydrogel could reduce the migration and proliferation of fibroblast cells in a dose-dependent manner. In summary, this study demonstrates the potential of a PFD-loaded injectable hydrogel with enhanced viscoelastic and tissue-adhesive properties for vocal fold scarring applications.

This chapter emphasizes the importance of suture design with respect to its clinical utility and specific application. The different engineering aspects of suture development have been categorized under structural, physical and biological attributes. These parameters have been explained in detail with examples of commercial sutures and scientific studies. The interdependence of these diverse attributes of suture design is also highlighted in this chapter. The last part focuses on the engineering constraints relevant to the development of drug-eluting sutures, which broadens the functionality of conventional sutures.

Biomedicalimplants possessing the structural and functional characteristicsof extracellular matrix (ECM) are pivotal for vascular applications.This study investigated the potential of recreating a natural ECM-likestructural and functional environment on the surface of biodegradablepolymeric nanotextiles for vascular implants. Human adipose-derivedmesenchymal stem cells (MSCs) were grown on a suitably engineeredpolycaprolactone (PCL) nanofibrous textile and were allowed to modifyits surface through the deposition of MSC-specific ECM. This surface-modifiednanotextile showed mechanical characteristics and functionality appropriatefor vascular patch material. The uniformity of ECM coating significantlyimproved the viability, proliferation, and migration of human endothelialcells compared to bare and xenogeneic collagen-coated PCL nanotextilepatches. Thus, a polymeric nanotextile, which is surface modifiedusing MSC-driven ECM, provided a rapid and improved endothelialization,thereby suggesting its potential for vascular patch applications.

Electrospinning technology has advanced significantly over the past two decades, and fibrous materials in multitudes of geometries, ranging from the conventional 2D membranes to 1D fiber bundles or yarns and recently 3D textile constructs have been developed. Of these, innovations in the engineering of electrospun fibers in the form of yarns, which circumvent the limitations of conventional electrospun fibers in terms of their mechanical characteristics, have emerged important. Nanoyarns which consist of thousands of nanofibers bundled together are advantageous because the fibers in yarns retain their nanoscale diameters required for functional benefit, but concurrently exhibit much improved mechanical properties that is key to the manufacturing of scaled-up products. This book chapter elucidates the innovations in nanofibrous yarn fabrication using DC and AC fields, diverse collector designs and modifications in the electrospinning assembly. The advantages and limitations of each of the methods utilized are discussed by highlighting the process yield, mechanical strength, scalability, and ease of fabrication. These nanofibrous yarns by retaining the functionality of fibers also meet the mechanical requirements of various textile processing techniques for developing scalable constructs. The chapter concludes with an overview on the diverse applications of electrospun nanoyarns, with emphasis in the field of biomedicine.

An imperative requisite of tissue-engineered scaffolds is to promote host cell regeneration and concomitantly thwart microbial growth. Antibacterial agents are often added to prevent implant-related infections, which, however, aggravates the risk of bacterial resistance. For the first time, we report a fiber-based platform that selectively promotes the growth of mammalian cells and alleviates bacteria by varying fiber size, orientation, and material of polymeric yarns. The interactions of Gram-positive and -negative bacterial species with mammalian mesenchymal stem cells (MSC) were investigated on poly-€-caprolactone (PCL) yarns, polyethylene terephthalate (PET), poly-L-lactic acid (PLLA), and cotton. Various yarn configurations were studied by altering the fiber diameter (from nano- to microscale) and fiber orientations (aligned, twisted, and random) of PCL yarns. PCL nanofibrous yarn decreased the adhesion of S. aureus and E. coli, with a 2.7-fold and 1.5-fold reduction, respectively, compared to PCL microfibrous yarn. Among different fiber orientations, nanoaligned fibers resulted in an 8-fold and 30-fold reduction of S. aureus and E. coli adhesion compared to random fibers. Moreover, aligned orientation was superior in retarding the S. aureus adhesion by 14-fold compared to nanotwisted fibers. Our data demonstrate that polymeric yarns comprising fibers with nanoscale features and aligned orientation promote mammalian cell adhesion and spreading and concomitantly mitigate bacterial interaction. Moreover, we unveil the wicking of cells through polymeric yarns, facilitating early cell adhesion in fibrous scaffolds. Overall, this study provides insight to engineer scaffolds that couple superior interaction of mammalian cells with high-strength fibrous yarns for regenerative applications devoid of antibacterial agents or other surface modification strategies.

A major impediment to the development of small diameter vascular grafts is to achieve an optimal balance between its mechanical properties and cellular response. To address this, the technique of cylindrical weaving has been combined with electrospinning to fabricate a seamless bilayered conduit (similar to 3 mm) having an inner cell-friendly nanofibrous layer of poly(caprolactone)/collagen and an outer mechanically compliant woven silk layer. Mechanical characteristics such as burst strength, suture retention, compliance and leak resistance were found to be improved for this bilayered conduit when compared to the commercial standard. In-vitro studies revealed that the lumen of the conduit was non-hemolytic and could support adhesion and viability of endothelial cells. Overall, our studies suggest that the proposed bilayer construct could be a suitable candidate for small diameter vascular prosthesis.

The current COVID-19 pandemic situation has posed a significant threat to human health. This calls for versatile facemask filters with high filtration efficiency and biocidal activity. Herein, we have rationally designed a three-layered nanofilter mask consisting of electrospun polycaprolactone (PCL) and curcumin as a nanocoating on a polypropylene spunbond membrane. The nanomask thus developed had a particulate filtration efficiency of 96.8 +/- 0.1%, with good breathability (64 +/- 2 Pa) and a high quality factor (0.052 +/- 0.0005 Pa-1) for a coating thickness of similar to 20 mu m. An aerosol filtration efficiency of >99.99% was achieved for both bacteria and bacteriophages (a virus surrogate). Curcumin loading into the nanocoating induced significant contact-killing efficiency against bacteria and bacteriophages, implying the high biocidal activity presented by the nanomask. Furthermore, this mask could be reused up to 30 times after successive washing and drying, without alterations in its particle-filtration efficiency or fibrous morphology. Thus, by adopting a simple, scalable technique, a nanomask with manifold features was developed that satisfies the essential demands of air filtration in the current pandemic era.

Mandible reconstruction and dental rehabilitation after trauma or tumor resection represent a serious challenge for maxillofacial surgeons. This study aimed to investigate the bone formation potential of nanocomposite fibrous scaffold (silica-nanohydroxyapatite-gelatin reinforced with poly L-lactic acid yarns - CSF) for delayed Titanium (Ti) implantation, which was compared to autograft (AG) taken from the iliac crest. The grafts were placed in critical-sized mandibular defects in an adult pig model for 6 months followed by dental implant placement for another 3 months. There was complete union and vascularised lamellar bone formation within 6 months. Moreover, the biological processes associated with angiogenesis, bone maturation and remodelling were seen in CSF, which was comparable to AG. Later, when Ti dental implant was placed on newly formed bone, CSF group demonstrated better osseointegration. In short, nanocomposite fibrous scaffold promoted quality bone formation in mandible defect that leads to successful osseointegration, suggesting as a potential candidate for implant-based rehabilitation in clinics in future.

Globally, millions of patients are affected by myocardial infarction or lower limb gangrene/amputation due to atherosclerosis. Available surgical treatment based on vein and synthetic grafts provides sub-optimal benefits. We engineered a highly flexible and mechanically robust nanotextile-based vascular graft (NanoGraft) by interweaving nanofibrous threads of poly-L-lactic acid to address the unmet need. The NanoGrafts were rendered impervious with selective fibrin deposition in the micropores by pre-clotting. The pre-clotted NanoGrafts (4 mm diameter) and ePTFE were implanted in a porcine carotid artery replacement model. The fibrin-laden porous milieu facilitated rapid endothelization by the transmural angiogenesis in the NanoGraft. In-vivo patency of NanoGrafts was 100% at 2- and 4-weeks, with no changes over time in lumen size, flow velocities, and minimal foreign-body inflammatory reaction. However, the patency of ePTFE at 2-week was 66% and showed marked infiltration, neointimal thickening, and poor host tissue integration. The study demonstrates the in-vivo feasibility and safety of a thin-layered vascular prosthesis, viz., NanoGraft, and its potential superiority over the commercial ePTFE.

Recent advances in coronary stents have all been distinctively focused towards directing re-endothelialization with minimal in-stent restenosis, potentially via alterations in surface topographical cues, for augmenting the efficacy of vascular implants. This perspective was proven by our group utilizing a simple and easily scalable nanosurface modification strategy on metallic stents devoid of any drugs or polymers. In the present work, we explore the impact of surface characteristics in modulating this cell response in-vitro and in-vivo, using titania coated cobalt-chromium (CC) stents, with and without nanotopography, in comparison to commercial controls. Interestingly, titania nanotopography facilitated a preferential cell response in-vitro as against the titania coated and bare CC surfaces, which can be attributed to surface topography, hydrophilicity, and roughness. This in turn altered the cellular adhesion, proliferation and focal contact formations of endothelial and smooth muscle cells. We also demonstrate that titania nanotexturing plays a pivotal role in fostering rapid re-endothelialization with minimal neointimal hyperplasia, leading to excellent in-vivo patency of CC stents post 8 weeks implantation in rabbit iliac arteries, in comparison to bare CC, nano-less titania coated CC, and commercial drug-eluting stents (CC DES), without administering antiplatelet agents. This exciting result for the drug and polymer-free titania nanotextured stents, in the absence of platelet therapy, reveals the possibility of proposing an alternative to clinical DES for coronary stenting.

BACKGROUNDDrug laden implantable systems can provide drug release over several hours to years, which eventually aid in the therapy of both acute and chronic diseases. The present study focuses on a fundamental evaluation of the influence of implant properties such as morphology, architecture, porosity, surface area, and wettability in regulating the drug release kinetics from drug-loaded polymeric matrices.METHODSFor this, Polydioxanone (PDS) was selected as the polymer and Paclitaxel (Ptx) as the model drug. Two different forms of the matrix implants, viz., reservoir type capsules developed by dip coating and matrix type membranes fabricated by phase inversion and electrospinning, were utilized for the study. Drug release from all the four different matrices prepared by simple techniques was evaluated in vitro in PBS and ex vivo in peritoneal wash fluid for ~4 weeks. The drug release profiles were thereafter correlated with the physicochemical parameters of the polymeric implants.RESULTSReservoir-type capsules followed a slow and steady zero-order kinetics, while matrix-type electrospun and phase inversion membranes displayed typical biphasic kinetics.CONCLUSIONIt was inferred that the slow degradation rate of PDS polymer as well as the implant properties like porosity and wettability play an important role in controlling the drug release rates.