Efficacy versus Toxicity - The Ying and Yang in Translating Nanomedicines

Nanomedicine, as a relatively new offshoot of nanotechnology, has presented vast opportunities in biomedical research for developing novel strategies to treat diseases. In the past decade, there has been a significant increase in in vitro and preclinical studies addressing the benefits of nanomedicines. In this commentary, we focus specifically on the efficacy- and toxicity-related translational challenges of nanocarrier-mediated systems, and briefly discuss possible strategies for addressing such issues at in vitro and preclinical stages. We address questions related specifically to the balance between toxicity and efficacy, a balance that is expected to be substantially different for nanomedicines compared to that for a free drug. Using case studies, we propose a ratiometric assessment tool to quantify the overall benefit of nanomedicine as compared to free drugs in terms of efficacy and toxicity. The overall goal of this commentary is to emphasize the strategies that promote the translation of nanomedicines, especially by learning lessons from previous translational failures of other drugs and devices, and to apply these lessons to critically assess data at the basic stages of nanomedicinal research

Effect of TiO₂ nanotube length and lateral tubular spacing on photovoltaic properties of back illuminated dye sensitized solar cell

The main objective of this study is to show the effect of TiO2 nanotube length, diameter and intertubular lateral spacings on the performance of back illuminated Dye Sensitized Solar Cells (DSSCs). The present study shows that processing short TiO2 nanotubes with good lateral spacings could significantly improve the performance of back illuminated DSSCs. Vertically aligned, uniform sized diameter TiO2 nanotube arrays of different tube lengths have been fabricated on Ti plates by a controlled anodization technique at different times of 24, 36, 48 and 72 h using ethylene glycol and ammonium fluoride as an electrolyte medium. Scanning Electron Microscopy (SEM) showed formation of nanotube arrays spread uniformly over a large area. X-ray Diffraction (XRD) of TiO2 nanotube layer revealed the presence of crystalline anatase phases. By employing the TiO2 nanotube array anodized at 24 h showing a diameter ∼80 nm and length ∼1•5 μm as the photo-anode for back illuminated DSSCs, a full-sun conversion efficiency (η) of 3•5% was achieved, the highest value reported for this length of nanotubes

Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration

Recently, scaffolds for tissue regeneration purposes have been observed to utilize nanoscale features in an effort to reap the cellular benefits of scaffold features resembling extracellular matrix (ECM) components. However, one complication surrounding electrospun nanofibers is limited cellular infiltration. One method to ameliorate this negative effect is by incorporating nanofibers into microfibrous scaffolds. This study shows that it is feasible to fabricate electrospun scaffolds containing two differently scaled fibers interspersed evenly throughout the entire construct as well as scaffolds containing fibers composed of two discrete materials, specifically fibrin and poly(?-caprolactone). In order to accomplish this, multiscale fibrous scaffolds of different compositions were generated using a dual extrusion electrospinning setup with a rotating mandrel. These scaffolds were then characterized for fiber diameter, porosity and pore size and seeded with human mesenchymal stem cells to assess the influence of scaffold architecture and composition on cellular responses as determined by cellularity, histology and glycosaminoglycan (GAG) content. Analysis revealed that nanofibers within a microfiber mesh function to maintain scaffold cellularity under serum-free conditions as well as aid the deposition of GAGs. This supports the hypothesis that scaffolds with constituents more closely resembling native ECM components may be beneficial for cartilage regeneration

A novel small diameter nanotextile arterial graft is associated with surgical feasibility and safety and increased transmural endothelial ingrowth in pig

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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-022-01268-1

Chitin Scaffolds in Tissue Engineering

Tissue engineering/regeneration is based on the hypothesis that healthy stem/progenitor cells either recruited or delivered to an injured site, can eventually regenerate lost or damaged tissue. Most of the researchers working in tissue engineering and regenerative technology attempt to create tissue replacements by culturing cells onto synthetic porous three-dimensional polymeric scaffolds, which is currently regarded as an ideal approach to enhance functional tissue regeneration by creating and maintaining channels that facilitate progenitor cell migration, proliferation and differentiation. The requirements that must be satisfied by such scaffolds include providing a space with the proper size, shape and porosity for tissue development and permitting cells from the surrounding tissue to migrate into the matrix. Recently, chitin scaffolds have been widely used in tissue engineering due to their non-toxic, biodegradable and biocompatible nature. The advantage of chitin as a tissue engineering biomaterial lies in that it can be easily processed into gel and scaffold forms for a variety of biomedical applications. Moreover, chitin has been shown to enhance some biological activities such as immunological, antibacterial, drug delivery and have been shown to promote better healing at a faster rate and exhibit greater compatibility with humans. This review provides an overview of the current status of tissue engineering/regenerative medicine research using chitin scaffolds for bone, cartilage and wound healing applications. We also outline the key challenges in this field and the most likely directions for future development and we hope that this review will be helpful to the researchers working in the field of tissue engineering and regenerative medicine

Integrating Substrateless Electrospinning with Textile Technology for Creating Biodegradable Three-Dimensional Structures

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

Integrating Substrateless Electrospinning with Textile Technology for Creating Biodegradable Three-Dimensional Structures

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

All spray pyrolysis-coated CdTe–TiO2 heterogeneous films for photo-electrochemical solar cells

Abstract Cadmium telluride (CdTe) thin films of different thicknesses deposited onto titanium dioxide (TiO2) nanoparticle layer by spray pyrolysis deposition (SPD) are demonstrated as major photo-active semiconductor in photo-electrochemical solar cell configuration using iodide/triiodide (I−/I3 −) redox couple as a hole transport layer. The CdTe–TiO2 heterogeneous films were characterized by X-ray photoelectron spectroscopy which identified doublet split of Cd 3d and Ti 2p which confirms CdTe and TiO2. Optical absorbance and transmittance of CdTe and TiO2 films which were examined by UV–Vis spectroscopy confirm that the optical bandgap of CdTe is 1.5 eV with a dominant photo-absorption in the spectral window of 350–800 nm, while TiO2 showed a bandgap of 3.1 eV and is optically transparent in the visible spectral window. The present work examined photo-anodes comprising 1, 3, 5, and 10 SPD cycles of CdTe coated on TiO2 nanoparticle layer. The solar cell with 5 SPD cycles of CdTe resulting in 0.4% efficiency. Results can be articulated to the CdTe deposited by 5 SPD cycles provided an optimum surface coverage in the bulk of TiO2, while the higher SPD cycles leads to agglomeration which blocks the porosity of the heterogeneous films