Hybrid Nanoparticle Engineered with Transforming Growth Factor -β1-Overexpressed Extracellular Vesicle and Cartilage-Targeted Anti-Inflammatory Liposome for Osteoarthritis.

Extracellular vesicles (EVs) possess the characteristics of their parent cells, based on which various studies have actively investigated treatments for diseases using mesenchymal stem cell-derived EVs due to their regenerative activity. Furthermore, in recent years, there have been significant efforts to engineer EVs to improve their native activities and integrate additional functions. Although both endogenous and exogenous methods are used for engineering EVs, endogenous methods may pose the problem of administering substances to cells undergoing metabolic changes, which can cause potential side effects.

Multifunctional extracellular vesicles and edaravone-loaded scaffolds for kidney tissue regeneration by activating GDNF/RET pathway.

With the severity of chronic kidney disease worldwide, strategies to recover renal function via tissue regeneration provide alternatives to kidney replacement therapy. To exclude side effects from direct cell transplantation, extracellular vesicles (EVs) are great substitutes representing paracrine cell signaling. To build three-dimensional structures for implantation into the 5/6 nephrectomy model by incorporating bioactive materials, including multifunctional EVs (mEVs), porous PMEZE/mEV scaffolds were developed in combination with edaravone (EDV; E) and mEV based on PMEZ scaffolds with PLGA (P), MH-RA (M), ECM (E), ZnO-ALA (Z).

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments.

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects.

Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection.

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs.

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease.

Introduction: With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging.

Objectives: To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds.

Kidney tissue regeneration using bioactive scaffolds incorporated with differentiating extracellular vesicles and intermediate mesoderm cells.

Background: To overcome the limitations of current alternative therapies for chronic kidney disease (CKD), tissue engineering-mediated regeneration strategies have demonstrated the possibilities for complete kidney tissue regeneration. Given the challenges associated with the reproducibility of renal basal cells, the incorporation of intermediate mesoderm (IM) cells and bioactive materials to control bioactivities of cells with supported scaffolds should be considered as a viable approach to enable the regeneration of the complex kidney structure via renal differentiation.

Methods: We developed PMEZ scaffolds by combining crucial bioactive components, such as ricinoleic acid-grafted Mg(OH) (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) integrated into biodegradable porous PLGA (P) platform.

Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media.

Human mesenchymal stem cells (hMSCs)-derived extracellular vesicles (EVs) have been known to possess the features of the origin cell with nano size and have shown therapeutic potentials for regenerative medicine in recent studies as alternatives for cell-based therapies. However, extremely low production yield, unknown effects derived from serum impurities, and relatively low bioactivities on doses must be overcome for translational applications. As several reports have demonstrated the tunability of secretion and bioactivities of EVs, herein, we introduced three-dimensional (3D) culture and cell priming approaches for MSCs in serum-free chemically defined media to exclude side effects from serum-derived impurities.

Endogenous stimulus-responsive nitric oxide releasing bioactive liposome for a multilayered drug-eluting balloon.

Drug-eluting balloon (DEB) system has been widely utilized for percutaneous coronary intervention (PCI), treating atherosclerosis to overcome the limitations of cardiovascular stents. With the anti-proliferative drug, everolimus (EVL), nitric oxide (NO) plays a key bioregulator role to facilitate the angiogenesis of endothelial cells (ECs) and inhibit the cell proliferation of smooth muscle cells (SMCs) in the lesions of cardiovascular diseases. Due to the very short lifetime and limited exposure area of NO in the body, the continuous release and efficient delivery of NO must be carefully considered.

The Upregulation of Regenerative Activity for Extracellular Vesicles with Melatonin Modulation in Chemically Defined Media.

Extracellular vesicles (EVs) derived from human mesenchymal stem cells (hMSCs) have been widely known to have therapeutic effects by representing characteristics of the origin cells as an alternative for cell-based therapeutics. Major limitations of EVs for clinical applications include low production yields, unknown effects from serum impurities, and relatively low bioactivities against dose. In this study, we proposed a cell modulation method with melatonin for human umbilical cord MSCs (hUCMSCs) cultured in serum-free chemically defined media (CDM) to eliminate the effects of serum-derived impurities and promote regeneration-related activities.

Comparative Analysis of MSC-Derived Exosomes Depending on Cell Culture Media for Regenerative Bioactivity.

Background: In order to produce and isolate the exosome derived from the cell of interests, a serum free environment (starvation) has been essential for excluding the unknown effect from serum-derived exosomes. Recently, serum-free culture media have been developed as a substitute for serum supplemented media so that MSC proliferates with maintaining the original characteristics of the cells in a serum free condition. Due to the different properties of the exosomes representing the states and characteristics of the origin cells, a study is needed to compare the properties of the cell-derived exosomes according to the cell culture media.

Defined MSC exosome with high yield and purity to improve regenerative activity.

Exosomes derived from mesenchymal stem cells (MSCs) have been studied as vital components of regenerative medicine. Typically, various isolation methods of exosomes from cell culture medium have been developed to increase the isolation yield of exosomes. Moreover, the exosome-depletion process of serum has been considered to result in clinically active and highly purified exosomes from the cell culture medium.

A Multilayer Functionalized Drug-Eluting Balloon for Treatment of Coronary Artery Disease.

Drug-eluting balloons (DEBs) have been mostly exploited as an interventional remedy for treating atherosclerosis instead of cardiovascular stents. However, the therapeutic efficacy of DEB is limited due to their low drug delivery capability to the disease site. The aim of our study was to load drugs onto a balloon catheter with preventing drug loss during transition time and maximizing drug transfer from the surface of DEBs to the cardiovascular wall.

Attenuation of Tumor Necrosis Factor-α Induced Inflammation by Umbilical Cord-Mesenchymal Stem Cell Derived Exosome-Mimetic Nanovesicles in Endothelial Cells.

Background: Inflammation induces dysfunction of endothelial cells via inflammatory cell adhesion, and this phenomenon and reactive oxygen species accumulation are pivotal triggers for atherosclerosis-related vascular disease. Although exosomes are excellent candidate as an inhibitor in the inflammation pathway, it is necessary to develop exosome-mimetic nanovesicles (NVs) due to limitations of extremely low release rate and difficult isolation of natural exosomes. NVs are produced in much larger quantities than natural exosomes, but due to the low flexibility of the cell membranes, the high loss caused by hanging on the filter membranes during extrusion remains a challenge to overcome.

Recent trends in cell membrane-cloaked nanoparticles for therapeutic applications.

Synthetic nanoparticles are extensively utilized in various biomedical engineering fields because of their unique physicochemical properties. However, their exogenous characteristics result in synthetic nanosystem invaders that easily induce the passive immune clearance mechanism, thereby increasing the retention effect caused by reticuloendothelial system (RES), resulting in low therapeutic efficacy and toxic effects. Recently, a cell membrane cloaking has been emerging technique as a novel interfacing approach from the biological/immunological perspective.

Dealloyed Intra-Nanogap Particles with Highly Robust, Quantifiable Surface-Enhanced Raman Scattering Signals for Biosensing and Bioimaging Applications.

Uniformly controlling a large number of metal nanostructures with a plasmonically enhanced signal to generate quantitative optical signals and the widespread use of these structures for surface-enhanced Raman scattering (SERS)-based biosensing and bioimaging applications are of paramount importance but are extremely challenging. Here, we report a highly controllable, facile selective-interdiffusive dealloying chemistry for synthesizing the dealloyed intra-nanogap particles (DIPs) with a ∼2 nm intragap in a high yield (∼95%) without the need for an interlayer. The SERS signals from DIPs are highly quantitative and polarization-independent with polarized laser sources.

Myoglobin and Polydopamine-Engineered Raman Nanoprobes for Detecting, Imaging, and Monitoring Reactive Oxygen Species in Biological Samples and Living Cells.

Highly reliable detection, imaging, and monitoring of reactive oxygen species (ROS) are critical for understanding and studying the biological roles and pathogenesis of ROS. This study describes the design and synthesis of myoglobin and polydopamine-engineered surface-enhanced Raman scattering (MP-SERS) nanoprobes with strong, tunable SERS signals that allow for specifically detecting and imaging ROS sensitively and quantitatively. The study shows that a polydopamine nanolayer can facilitate the modification of Raman-active myoglobins and satellite Au nanoparticles (s-AuNPs) to a plasmonic core AuNP (c-AuNP) in a controllable manner and the generation of plasmonically coupled hot spots between a c-AuNP and s-AuNPs that can induce strong SERS signals.

Synthesis, Optical Properties, and Multiplexed Raman Bio-Imaging of Surface Roughness-Controlled Nanobridged Nanogap Particles.

Plasmonic nanostructures are widely studied and used because of their useful size, shape, composition and assembled structure-based plasmonic properties. It is, however, highly challenging to precisely design, reproducibly synthesize and reliably utilize plasmonic nanostructures with enhanced optical properties. Here, we devise a facile synthetic method to generate Au surface roughness-controlled nanobridged nanogap particles (Au-RNNPs) with ultrasmall (≈1 nm) interior gap and tunable surface roughness in a highly controllable manner.

Oxidative nanopeeling chemistry-based synthesis and photodynamic and photothermal therapeutic applications of plasmonic core-petal nanostructures.

The precise control of plasmonic nanostructures and their use for less invasive apoptotic pathway-based therapeutics are important but challenging. Here, we introduce a highly controlled synthetic strategy for plasmonic core-petal nanoparticles (CPNs) with massively branched and plasmonically coupled nanostructures. The formation of CPNs was facilitated by the gold chloride-induced oxidative disassembly and rupture of the polydopamine corona around Au nanoparticles and subsequent growth of Au nanopetals.

Glutathione dimerization-based plasmonic nanoswitch for biodetection of reactive oxygen and nitrogen species.

Reactive oxygen and nitrogen species (ROS and RNS) are continuously produced in the cellular systems and are controlled by several antioxidant mechanisms. Here, we developed a straightforward, sensitive, and quantitative assay for the colorimetric and spectroscopic detection of various ROS and RNS such as H2O2, ·OH, (-)OCl, NO·, and O2(-) using glutathione-modified gold nanoparticles (GSH-AuNPs). A basic principle here is that the GSHs on the AuNP surface can be readily detached via the formation of glutathione disulfides upon the addition of ROS and RNS, and destabilized particles can aggregate to generate the plasmonic couplings between plasmonic AuNPs that trigger the red shift in UV-vis spectrum and solution color change.

Tumor targeting and imaging using cyclic RGD-PEGylated gold nanoparticle probes with directly conjugated iodine-125.

Radioactive iodine-labeled, cyclic RGD-PEGylated gold nanoparticle (AuNP) probes are designed and synthesized for targeting cancer cells and imaging tumor sites. These iodine-125-labeled cRGD-PEG-AuNP probes are stable in various conditions including a range of pHs and high salt and temperature conditions. These probes can target selectively and be taken up by tumor cells via integrin αvβ3-receptor-mediated endocytosis with no cytotoxicity.