Adhesion strategies that rely on mechanical interlocking or molecular attractions between surfaces can suffer when coming into contact with liquids. Thus far, artificial wet and dry adhesives have ...included hierarchical mushroom-shaped or porous structures that allow suction or capillarity, supramolecular structures comprising nanoparticles, and chemistry-based attractants that use various protein polyelectrolytes. However, it is challenging to develop adhesives that are simple to make and also perform well-and repeatedly-under both wet and dry conditions, while avoiding non-chemical contamination on the adhered surfaces. Here we present an artificial, biologically inspired, reversible wet/dry adhesion system that is based on the dome-like protuberances found in the suction cups of octopi. To mimic the architecture of these protuberances, we use a simple, solution-based, air-trap technique that involves fabricating a patterned structure as a polymeric master, and using it to produce a reversed architecture, without any sophisticated chemical syntheses or surface modifications. The micrometre-scale domes in our artificial adhesive enhance the suction stress. This octopus-inspired system exhibits strong, reversible, highly repeatable adhesion to silicon wafers, glass, and rough skin surfaces under various conditions (dry, moist, under water and under oil). To demonstrate a potential application, we also used our adhesive to transport a large silicon wafer in air and under water without any resulting surface contamination.
High adhesion and water resistance on skin surfaces are highly demanded properties for wearable and skin‐attachable electronics in various medical applications. Here, stretchable electronics with ...octopus‐like patterns (OPs) imprinted on a carbon‐based conductive polymer composite (CPC) film are presented. The bioinspired conductive suckers with dome‐like architectures are successfully exploited to sustain weight (500 g) in underwater, wherein this performance is known to be challenging. In addition, the artificial patch allows highly adhesive capabilities under both dry and wet conditions on various surfaces such as silicon (max. 5.24 N cm−2) and skin replica (max. 1.89 N cm−2) without contamination after detachment with an effortless peel‐off technique. The resulting device with low volumetric ratio of conductive carbon black presents sensitive and reliable piezoresistive responses to lateral strain and vertical pressure. By controlling the ratio of the carbon nanoplatelets in the polymeric matrix, electronic patch demonstrates both detection of electrocardiogram (ECG) and bending motions of wrist in dry and wet environments. Based on the characteristics shown in this work, the proposed electronic patch is a promising approach to realize wearable and skin‐attachable sensor devices for in vitro and in vivo monitoring of various biosignals.
Skin‐attachable and water‐resistant stretchable electronics are fabricated by employing an array of octopus‐like patterns on conductive polymer composite films. The electronic patch is not only highly sensitive to strain and pressure, but also strongly adhesive on dry and wet surfaces due to the suction effect. Finally, the device demonstrates measurements of biosignals and bending motions in underwater environments.
Inorganic nanoparticles (NPs) offer significant advantages to the biomedical field owing to their large surface area, controllable structures, diverse surface chemistry, and unique optical and ...physical properties. Researchers worldwide have shown that inorganic NPs and the released metal ions can act as therapeutic agents in targeted tissues or to cure various diseases without acute toxicity. In this progress report, the recent developments in inorganic NPs with different compositions directly used as therapeutics are discussed. First, the recent convergence of nanotechnology and biotechnology in biomedical applications as well as the unique functions, features, and advantages of inorganic NPs in biomedical applications are summarized. Thereafter, the biological effects of inorganic compositions in NPs which include balancing the intracellular redox environment, regulating the specific cellular signaling and cellular behaviors, and apoptosis are explained. In addition, the emerging therapeutic applications of inorganic NPs in various diseases are exemplified. Finally, the perspectives and challenges for overcoming the weaknesses of inorganic NPs as therapeutics are discussed. By carefully considering and investigating the biological effects of inorganic NPs and metal ions released from NPs, more promising inorganic NPs based therapeutic agents can be developed.
This progress report discusses the recent developments of the therapeutic effects and application of inorganic nanoparticles. The nanoparticles or released ions can be used to enhance the therapeutic effects of certain treatment strategies, regulate the reactive oxygen species levels, and interfere with specific cellular signaling pathways and behaviors, which benefit both cancer treatment and recovery from other diseases.
Here, it is shown that graphene oxide (GO) can be utilized as both a cell‐adhesion substrate and a growth factor protein‐delivery carrier for the chondrogenic differentiation of adult stem cells. ...Conventionally, chondrogenic differentiation of stem cells is achieved by culturing cells in pellets and adding the protein transforming growth factor‐β3 (TGF‐β3), a chondrogenic factor, to the culture medium. However, pellets mainly provide cell‐cell interaction and diffusional limitation of TGF‐β3 may occur inside the pellet both of these factors may limit the chondrogenic differentiation of stem cells. In this study, GO sheets (size = 0.5–1 μm) were utilized to adsorb fibronectin (FN, a cell‐adhesion protein) and TGF‐β3 and were then incorporated in pellets of human adipose‐derived stem cells (hASCs). The hybrid pellets of hASC‐GO enhanced the chondrogenic differentiation of hASCs by adding the cell‐FN interaction and supplying TGF‐β3 effectively. This method may provide a new platform for stem cell culture for regenerative medicine.
Graphene oxide can be used as both a cell‐adhesion substrate and a growth factor delivery carrier for the chondrogenic differentiation of adult stem cells.
As a tissue regeneration strategy, the utilization of mesenchymal stem cells (MSCs) has drawn considerable attention. Comprehensive research using MSCs has led to significant preclinical or clinical ...outcomes; however, improving the survival rate, engraftment efficacy, and immunogenicity of implanted MSCs remains challenging. Although MSC-derived exosomes were recently introduced and reported to have great potential to replace conventional MSC-based therapeutics, the poor production yield and heterogeneity of exosomes are critical hurdles for their further applications. Herein, we report the fabrication of exosome-mimetic MSC-engineered nanovesicles (MSC-NVs) by subjecting cells to serial extrusion through filters. The fabricated MSC-NVs exhibit a hydrodynamic size of ~120 nm, which is considerably smaller than the size of MSCs (~30 μm). MSC-NVs contain both MSC markers and exosome markers. Importantly, various therapeutic growth factors originating from parent MSCs are encapsulated in the MSC-NVs. The MSC-NVs exerted various therapeutic effects comparable to those of MSCs. They also significantly induced the angiogenesis of endothelial cells and showed neuroprotective effects in damaged neuronal cells. The results collectively demonstrate that the fabricated MSC-NVs can serve as a nanosized therapeutic agent for tissue regeneration.
A cancer‐selective self‐reporting sensor based on a redox‐responsive mineralized conductive hydrogel (M‐Hydrogel) is proposed with cancer‐specific viscosity, adhesive strength, stretchability, ...tunable conductivity, and fluorescence. The redox‐triggered release of carbonized polydopamine (cPDA) from the loaded disulfide‐crosslinked polymer dots (PD@cPDA) in the hydrogel matrix modulates the macroporous structure responsible for self‐recognizable cancer sensing and photothermal activity for cancer therapy. The self‐reporting nature of the M‐Hydrogel sensor is highlighted when in vicinity of a high glutathione (GSH) level owing to the controllable pore size and H‐bonding by cPDA, as confirmed by experiments on cancer cells (HeLa, PC3, B16‐F10‐GFP, and SNU‐C2A) and normal cells (CHO‐K1). The lower viscosity during syringe test along with the exceptional adhesiveness and stretchability with various cancer cells, combined with a high wireless pressure‐sensing response absent in normal conditions, confirms the dependence of self‐recognizable behavior on the cancer microenvironment. The M‐Hydrogel demonstrates excellent ex situ sensing with tumor ablation, after implantation in mice xenografted with HeLa cells, with the wireless sensing system, enabling real‐time analysis coupled with the upregulation of pro‐apoptotic markers P53 and BAX in the tumor. Therefore, this self‐reporting sensor may facilitate a strategy for innovative and convenient cancer diagnostics.
A self‐reporting mineralized hydrogel sensor demonstrating cancer detection via cancer‐selective injectability, viscosity change, adhesiveness, and stretchability, is developed in conjunction with a wireless conductive response. In vivo, the sensor displays good therapeutic performance with tumor ablation via selective photothermal heat generation, which in combination with the ex situ wireless sensing system allows real‐time analysis resulting in accurate diagnosis of cancer.
Current treatments for wound healing engage in passive healing processes and rarely participate in stimulating skin cell behaviors for active wound healing. Electric potential difference‐derived ...electrical fields (EFs) are known to modulate skin cell behaviors. Here, a piezoelectric dermal patch is developed that can be applied on skin wound site and EF is generated to promote wound healing. The one‐directionally aligned zinc oxide nanorod‐based piezoelectric patch generates piezoelectric potential upon mechanical deformations induced by animal motion, and induces EF at the wound bed. In vitro and in vivo data demonstrate that the piezoelectric patch promotes the wound healing process through enhanced cellular metabolism, migration, and protein synthesis. This modality may lead to a clinically relevant piezoelectric dermal patch therapy for active wound healing.
A piezoelectric patch that can be applied on skin wounds and generate electric fields (EFs) to promote wound healing is developed. The zinc oxide nanorod‐based patch generates piezoelectric potential upon skin movements, and induces EF at the wound bed. In vitro and in vivo data suggest the patch promotes skin regeneration through enhanced cellular metabolism, migration, and protein synthesis.
All exogenous nanomaterials undergo rapid biotransformation once injected into the body and fall short of executing the intended purpose. Here, it is reported that copper‐deposited ceria ...nanoparticles (CuCe NPs) exhibit enhanced antioxidant effects over pristine ceria nanoparticles, as the released copper buffers the depletion of glutathione while providing the bioavailable copper as a cofactor for the antioxidant enzyme, superoxide dismutase 1. The upregulated intracellular antioxidants along with the ceria nanoparticles synergistically scavenge reactive oxygen species and promote anti‐inflammation and M2 polarization of macrophages by modulating signal transducer and activator of transcription 1 and 6 (STAT1 and STAT6). The therapeutic effect of CuCe NPs is demonstrated in ischemic vascular diseases (i.e., murine models of hindlimb ischemia and myocardial infarction) in which the copper‐deposition affords increased perfusion and alleviation in tissue damage. The results provide rationale that metal oxide nanomaterials can be designed in a way to induce the upregulation of specific biological factors for optimal therapeutic performance.
Ceria nanoparticles deposited with copper ions, cofactors for the indigenous antioxidant enzyme, superoxide dismutase 1 (SOD1), are synthesized for effective and synergistic antioxidant therapy to treat ischemic vascular diseases in which the imbalance of reactive oxygen species (ROS) aggravates the tissue damage. Ceria nanoparticles chaperone copper ions to elevate the expression of SOD1 to significantly reduce the ROS‐induced damage.
Piezocatalytic cancer therapy, in which piezoelectric nanomaterials generate reactive oxygen species (ROS) via piezocatalytic redox reactions under mechanical stress, has emerged as an effective ...strategy for cancer treatment. However, the inherent hypoxia in tumor microenvironments enormously restricts its efficacy. To address this issue, acid‐degradable Janus‐type multicompartmental carriers able to separately encapsulate piezocatalytic gold nanoparticle‐coated poly(ethylene glycol)‐modified zinc oxide nanorods (Au@P‐ZnO NRs) and O2‐generating catalase (CAT) are fabricated in this study using stop‐flow lithography (SFL). The CAT and Au@P‐ZnO NRs are sequentially released by modulating the composition ratios of acid‐cleavable monomers in the precursor solution during the SFL. The sequential release by the Janus carriers significantly increased the intracellular ROS levels under hypoxia conditions upon ultrasound irradiation owing to the O2 supplied by the CAT. An in vivo study showed that a single intratumoral injection of Janus particles encapsulating the CAT and Au@P‐ZnO NRs efficiently alleviated tumor hypoxia and substantially suppressed tumor growth. This study demonstrates that pH‐responsive, O2‐generating, and piezocatalytic Janus carriers have high potential for piezocatalytic therapy of hypoxic tumors and offers insights into using pH‐responsive Janus carriers for efficient hypoxia‐relieving piezocatalytic cancer therapy via the cascade of oxygenation and ROS generation.
pH‐responsive Janus‐type multicompartmental carriers encapsulating piezocatalytic Au@P‐ZnO NRs and O2‐generating natural catalase (CAT) in separate compartments are developed for ultrasound‐triggered, hypoxia‐relieving, tumor‐targeted piezocatalytic therapy. The Janus carriers enable the sequential release of the CAT (Step I) and Au@P‐ZnO NRs (Step II) under acidic tumor microenvironments and thus efficiently eradicate hypoxic tumors under ultrasound irradiation via the cascade of oxygenation and ROS generation.
Abstract Stem cells offer significant therapeutic promise for the treatment of ischemic disease. However, stem cells transplanted into ischemic tissue exhibit limited therapeutic efficacy due to poor ...engraftment in vivo . Several strategies for improving the survival and engraftment of stem cells in ischemic tissue have been developed including transplantation in combination with growth factor delivery, genetic modification of stem cells, and the use of cell-transplantation scaffolds. Here, we demonstrate that human adipose-derived stromal cells (hADSCs) cultured and grafted as spheroids exhibit improved therapeutic efficacy for ischemia treatment. hADSCs were cultured in monolayer or spheroids. Spheroid cultures were more effective in preconditioning hADSCs to a hypoxic environment, upregulating hypoxia-adaptive signals (i.e., stromal cell-derived factor-1α and hypoxia-inducible factor-1α), inhibiting apoptosis, and enhancing secretion of both angiogenic and anti-apoptotic factors (i.e., hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor 2) compared to monolayer cultures. Moreover, cell harvesting following spheroid cultures avoided damage to extracellular matrices due to harsh proteolytic enzyme treatment, thereby preventing anoikis (apoptosis induced by a lack of cell–matrix interaction). Following intramuscular transplantation to ischemic hindlimbs of athymic mice, hADSC spheroids showed improved cell survival, angiogenic factor secretion, neovascularization, and limb survival as compared to hADSCs grafted as dissociated cells. Taken together, spheroid cultures precondition hADSCs to a hypoxic environment, and grafting hADSCs as spheroids to ischemic limbs improves therapeutic efficacy for ischemia treatment due to enhanced cell survival and paracrine effects. Spheroid-based cell delivery could be a simple and effective strategy for improving stem cell therapy for ischemic diseases, eliminating the need for growth factor delivery, biomaterial scaffolds or genetic modification.
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