Thermal-Responsive Gel-Based Overheat Limiter Enabled Intelligent Photothermal Therapy.

Uncontrolled and excessive photothermal heating in photothermal therapy (PTT) inevitably causes thermal damage to surrounding normal tissues, severely limiting the universality and safety of PTT. To address this issue, an intelligent cooling thermal-responsive (ICTR) gel containing poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-AM))microgel is applied onto the skin to realize intelligent PTT, which can avoid excessive heating and accidental injury. The high near-infrared (NIR) light transmittance (> 95%) of the ICTR gel ensures effective light delivery at low temperatures, while the refractive index of the P(NIPAM-AM) microgel increases remarkably when the temperature exceeds a predetermined threshold, resulting in progressively enhanced light scattering and weakened photothermal conversion. In animal studies, the negative feedback regulation of ICTR gel on light transmittance and photothermal heating allows the photothermal temperature in the lesion site to be stabilized within the effective therapeutic range (45 °C) while ensuring that the skin surface temperature does not exceed 35 °C. Compared with the severe skin thermal damage found in the histological staining of mice skin receiving conventional PTT, the mice skin receiving the ICTR gel-enabled intelligent PTT remains in good condition. This study establishes an intelligent and universal paradigm for PTT thermal regulation, which is of great significance for achieving safe and effective PTT.

Deepened Photodynamic Therapy through Skin Optical Clearing Technology in the Visible Light Window.

The trade-off that shorter wavelength light facilitates the efficient generation of reactive oxygen species (ROS) from photosensitizer (PS) while facing the drawback of limited penetration depth through skin tissue restricts the further development of photodynamic therapy (PDT). Here, we address this contradiction and achieve visible-light-tailored deep PDT combined with the skin optical clearing technology. With the help of the prepared skin optical clearing gel, the refractive index inhomogeneity between skin tissue components is greatly attenuated, and the light scattering effect within the skin tissue is remarkably reduced. As a consequence, the transmittance of visible light at 600 nm through in vitro porcine skin and in vivo mouse skin after treatment increases from approximately 10 and 40 to 70 and 70%, respectively. Furthermore, in the tumor cell eradication experiment, the local ROS generation efficiency in the experimental group is several times higher than that in the control group owing to improved visible transmittance, which is thus responsible for the complete eradication of tumor cells, even when shaded by skin tissue. The results suggest that this strategy may serve as a valuable supplement to the current deep PDT strategies.

Floating Hydrogel Beads Made by Droplet Impact.

Droplet impact is a ubiquitous natural phenomenon that has been widely utilized to inspire and facilitate many industrial applications. Compared to the widely studied water droplet impact onto identical liquid surfaces, the water droplet impact onto an oil layer floating on a water bath (OLW) receives far less attention and its potential application has never been exploited. Herein, the process of water droplet impact onto the OLW is investigated with emphasis on the metastable states and potential applications. It is found that the dramatic deformation of the oil-water interface caused by the water droplet impact leads to two metastable states: oil in water in oil in water (O/W/O/W) and oil in water in oil (O/W/O). Through the subsequent introduction of gelation process, the metastable states can be frozen into floating hydrogel beads with similar shape to the roly-poly toys, which are attempted in gastric retentive drug delivery and algae bloom control. Specifically, the floating hydrogel beads perform well in gastric retentive drug delivery in vitro due to their inherent slow-release properties and floating capability. In addition, the floating hydrogel beads loading photocatalysts can capture more sunshine, and exhibit high photocatalytic efficiency, which is thus responsible for efficient algae bloom control.

Ultradeep Photothermal Therapy Strategies.

Photothermal therapy (PTT) mediated by the second near-infrared light (NIR-II) is considered as the most promising PTT in deep tissues due to the superior penetrability of NIR-II through biological tissues. However, the effective therapeutic depth of NIR-II mediated PTT is limited to only several millimeters beneath the skin tissues. So far, deep PTT still cannot satisfy the depth requirement for most common cancers, including but not limited to lung, pancreatic, colorectal, and stomach cancers. Therefore, it is highly desirable to develop ultradeep PTT strategies to enhance the therapeutic depth with clinical availability. This Perspective highlights the latest research progress in regard to ultradeep PTT strategies, including larger laser spot PTT, skin tissue optical clearing technology enhanced PTT, and optical fiber assisted PTT, followed with pertinent evaluations and expectations. In addition, challenges and perspectives in this fast-growing area of ultradeep PTT are discussed.

Artificial Kidney Capsule Packed with Mesenchymal Stem Cell-Laden Hydrogel for the Treatment of Rhabdomyolysis-Induced Acute Kidney Injury.

Acute kidney injury (AKI) has emerged as a major public health problem affecting millions of people worldwide without specific and satisfactory therapies due to the lack of an effective delivery approach. In the past few decades, hydrogels present infinite potential in localized drug delivery, while their poor adhesion to moist tissue and isotropic diffusion character always restrict the therapeutic efficiency and may lead to unwanted side effects. Herein, we proposed a novel therapeutic strategy for AKI via a customizable artificial kidney capsule (AKC) together with a mesenchymal stem cell (MSC)-laden hydrogel. Specifically, an elastic capsule owning an inner chamber with the same size and shape as the kidney is designed and fabricated through three-dimensional (3D) modeling and printing, serving as an outer wrap for kidney and cell-laden hydrogels. According to the in vitro experiment, the excellent biocompatibility of gelatin-based hydrogel ensures viability and proliferation of MSCs. In vivo mice experiments proved that this concept of AKC-assisted kidney drug delivery could efficiently reduce epithelial cell apoptosis and minimize the damage of the renal tubular structure for mice suffering AKI. Such a strategy not only provides a promising alternative in the treatment of AKI but also offers a feasible and versatile approach for the repair and recovery of other organs.

An Ultra-Low-Temperature Elastomer with Excellent Mechanical Performance and Solvent Resistance.

Elastomers presenting good elasticity, ductility, and chemical resistance at low temperatures can serve as superior performers for explorations in extremely cold environments. However, no commercially available elastomer to date can comprehensively fulfill those demands. Here, a perfluoropolyether (PFPE)-based network crosslinked by dynamic urethane chemistry is demonstrated, which may satisfy the demands of application in ultracold environments. As the crucial constitute in such a crosslinked network, PFPE provides the elastomer with excellent elasticity at a temperature down to -110 °C and outstanding ductility within the cryogenic temperature range. Importantly, the high proportion of fluorocarbon segment also provides wonderful compatibility to most organic solvents, accounting for the low-swelling characteristics of the elastomer in sealing applications. Furthermore, the dynamic crosslinking feature allows the cured elastomer to be reprocessed like thermoplastic polymers, which affords great promise to recycle and reuse the elastomer after its disposal. Inherently, this elastomer would inspire a worldwide interest in the design of elastic devices that are adaptable to extremely low temperature.

Ionic Network Based on Dynamic Ionic Liquids for Electronic Tattoo Application.

Electronic tattoos as an emerging epidermal electronic are alluring in the field of wearable electronics for their lightweight and noninvasive properties. However, the combination of flexibility, skin biocompatibility, adhesion, repairability, and erasability remains a challenge for fabricating electronic tattoos. Hence, a dynamic ionic liquid is prepared which is ideally suited for making an electronic tattoo with these challenging features at the same time. Such an intrinsically flexible electronic tattoo can be firmly attached to human skin with negligible irritation. More importantly, the existence of dynamic covalent chemistry provides the electronic tattoo with healing and erasable abilities under mild redox conditions. Owing to the high ionic conductivity of ionic liquids, the electronic tattoo exhibits excellent sensing performance in response to the temperature variation and tensile strain, which can intelligently monitor body temperature, pulse, and movement. As an extension of the application, a specially designed quadrilateral electronic tattoo can sense and distinguish multiple signals simultaneously. This concept of electronic tattoo based on the dynamic ionic liquid shows great potentials in the applications of intelligent wearable electronics.

An injectable bioink with rapid prototyping in the air andin-situmild polymerization for 3D bioprinting.

Bioprinting is an attractive technology for building tissues from scratch to explore entire new cell configurations, which brings numerous opportunities for biochemical research such as engineering tissues for therapeutic tissue repair or drug screening. However, bioprinting is faced with the limited number of suitable bioinks that enable bioprinting with excellent printability, high structural fidelity, physiological stability, and good biocompatibility, particularly in the case of extrusion-based bioprinting. Herein, we demonstrate a composite bioink based on gelatin, bacterial cellulose (BC), and microbial transglutaminase (mTG enzyme) with outstanding printing controllability and durable architectural integrity. BC, as a rheology modifier and mechanical enhancer component, endows the bioink with shear-thinning behavior. Moreover, the printed structure becomes robust under physiological conditions owing to thein situchemical crosslinking catalyzed by mTG enzyme. Lattice, bowl, meniscus, and ear structures are printed to demonstrate the printing feasibility of such a composite bioink. Furthermore, the 3D-printed cell-laden constructs are proved to be a conducive biochemical environment that supports growth and proliferation of the encapsulated cellsin vitro. In addition, thein vivostudies convince that the composite bioink possesses excellent biocompatibility and biodegradation. It is believed that the innovation of this new composite bioink will push forward the bioprinting technology onto a new stage.

Three Birds with One Stone: Injectable CaC2 Nanobombs with Triple Effects for Minimally Invasive Tumor Chemical Ablation.

Percutaneous chemical ablation (PCA) is the oldest and most established technique for treating small solid tumors in organs. It has been widely used in clinics even on an outpatient basis. However, compared with the emerging microwave or magnetic hyperthermal ablation, PCA is faced with relatively poor necrosis results and needs to repeat multiple sessions. Inspired by the three effects in the bomb's explosive process, we herein expect to combine calcium carbide (CaC2) nanoparticles into the PCA technique to generate local explosion within tumor tissues, leading to three killing effects against tumors to further improve the ablation efficacy of PCA. Through an efficient wet milling procedure with poly(ethylene glycol), three kinds of nanobombs including CaC2, calcium oxide (CaO), and calcium hydroxide (Ca(OH)2) were fabricated, and they all exhibited desirable suspension stability. Among these nanobombs, in particular CaC2 nanobombs showed a synergistic effect that the generation of ethyne gas bubbles could facilitate the most rapid diffusion of hyperthermia. Also, CaC2 nanobombs offered the powerful ability to cause the sudden rise of local high temperature and pH value. According to the in vivo mice tumor excision trial, the tumors of 75% of cases that received CaC2 treatment were destroyed and eradicated, exhibiting the excellent ablation ability of CaC2 nanobombs against small solid tumors planted in mice.