Nanomaterials with intrinsic enzyme-like activities (nanozymes), have been widely used as artificial enzymes in biomedicine. However, how to control their in vivo performance in a target cell is still challenging. Here we report a strategy to coordinate nanozymes to target tumor cells and selectively perform their activity to destruct tumors. We develop a nanozyme using nitrogen-doped porous carbon nanospheres which possess four enzyme-like activities (oxidase, peroxidase, catalase and superoxide dismutase) responsible for reactive oxygen species regulation. We then introduce ferritin to guide nitrogen-doped porous carbon nanospheres into lysosomes and boost reactive oxygen species generation in a tumor-specific manner, resulting in significant tumor regression in human tumor xenograft mice models. Together, our study provides evidence that nitrogen-doped porous carbon nanospheres are powerful nanozymes capable of regulating intracellular reactive oxygen species, and ferritinylation is a promising strategy to render nanozymes to target tumor cells for in vivo tumor catalytic therapy.

Mimicking soft tissue mechanical properties and the high conductivity required for electrical transmission in the native spinal cord is critical in nerve tissue regeneration scaffold designs. However, fabricating scaffolds of high conductivity, tissue-like mechanical properties, and excellent biocompatibility simultaneously remains a great challenge. Here, a soft, highly conductive, biocompatible conducting polymer hydrogel (CPH) based on a plant-derived polyphenol, tannic acid (TA), cross-linking and doping conducting polypyrrole (PPy) chains is developed to explore its therapeutic efficacy after a spinal cord injury (SCI). The developed hydrogels exhibit an excellent electronic conductivity (0.05–0.18 S/cm) and appropriate mechanical properties (0.3–2.2 kPa), which can be achieved by controlling TA concentration. In vitro, a CPH with a higher conductivity accelerated the differentiation of neural stem cells (NSCs) into neurons while suppressing the development of astrocytes. In vivo, with relatively high conductivity, the CPH can activate endogenous NSC neurogenesis in the lesion area, resulting in significant recovery of locomotor function. Overall, our findings evidence that the CPHs without being combined with any other therapeutic agents have stimulated tissue repair following an SCI and thus have important implications for future biomaterial designs for SCI therapy.

Background: This study aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosome injection on cartilage damage and pain relief in both in vitro and in vivo models of osteoarthritis (OA). Methods: The BMSCs were extracted from rat bone marrow of the femur and tibia. Chondrocytes were treated with IL-1β to establish the in vitro model of OA. Chondrocyte proliferation and migration were assessed by CCK-8 and transwell assay, respectively. A rat model of OA was established by injection of sodium iodoacetate. At 6 weeks after the model was established, the knee joint specimens and dorsal root ganglion (DRG) of rats were collected for histologic analyses. For pain assessment, paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were evaluated before model establishment and at 1, 2, 4, and 6 weeks after model establishment. Results: Exosomes can be endocytosed with the chondrocytes in vitro. Exosome treatment significantly attenuated the inhibitory effect of IL-1β on the proliferation and migration of chondrocytes. Exosome pre-treatment significantly attenuated IL-1β-induced downregulation of COL2A1 and ACAN and upregulation of MMP13 and ADAMTS5. In the animal study, exosome treatment significantly upregulated COL2A1 protein and downregulated MMP13 protein in the cartilage tissue of the OA rat. At weeks 2, 4, and 6, the PWL value was significantly improved in the exosome-treated OA rats as compared with the untreated OA animals. Moreover, exosome treatment significantly alleviated the upregulation of CGRP and iNOS in the DRG tissue of OA rats. Conclusion: BMSC-derived exosomes can effectively promote cartilage repair and extracellular matrix synthesis, as well as alleviate knee pain in the OA rats.

Biocompatible hydrogel adhesives with multifunctional properties, including injectability, fast self-healing, and suitable on-demand detachment, are highly desired for minimally invasive procedures, but such materials are still lacking. Herein, an injectable self-healing biocompatible hydrogel adhesive with thermoresponsive reversible adhesion based on two extracellular matrix-derived biopolymers, gelatin and chondroitin sulfate, is developed to be used as a surgical adhesive for sealing or reconnecting ruptured tissues. The resulting hydrogels present good self-healing and can be conveniently injected through needles. The strong tissue adhesion at physiological temperatures originates from the Schiff base and hydrogen bonding interactions between the hydrogel and tissue that can be weakened at low temperatures, thereby easily detaching the hydrogel from the tissue in the gelation state. In vivo and ex vivo rat model show that the adhesives can effectively seal bleeding wounds and fluid leakages in the absence of sutures or staples. Specifically, a proof of concept experiment in a damaged rat liver model demonstrates the ability of the adhesives to act as a suitable laparoscopic sealant for laparoscopic surgery. Overall, the adhesive has several advantages, including low cost and ease of production and application that make it an exceptional multifunctional tissue adhesive/sealant, effective in minimally invasive surgical applications.

Metal–carbon hybrid materials have shown promise as potential enzyme mimetics for antibacterial therapy; however, the effects of metal states and corresponding antibacterial mechanisms are largely unknown. Here, two kinds of copper/carbon nanozymes were designed, with tuned copper states from Cu0 to Cu2+. Results revealed that the copper/carbon nanozymes exhibited copper state-dependent peroxidase-, catalase-, and superoxide dismutase-like activities. Furthermore, the antibacterial activities were also primarily determined by the copper state. The different antibacterial mechanisms of these two copper/carbon nanozymes were also proposed. For the CuO-modified copper/carbon nanozymes, the released Cu2+ caused membrane damage, lipid peroxidation, and DNA degradation of Gram-negative bacteria, whereas, for Cu-modified copper/carbon nanozymes, the generation of reactive oxygen species (ROS) via peroxidase-like catalytic reactions was the determining factor against both Gram-positive and Gram-negative bacteria. Lastly, we established two bacterially infected animal models, i.e., bacteria-infected enteritis and wound healing, to confirm the antibacterial ability of the copper/carbon nanozymes. Our findings provide a deeper understanding of metal state-dependent enzyme-like and antibacterial activities and highlight a new approach for designing novel and selective antibacterial therapies based on metal–carbon nanozymes.

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair.

Current treatment approaches for spinal cord injuries (SCIs) are mainly based on cellular transplantation. Induced pluripotent stem cells (iPSCs) without supply constraints and ethical concerns have emerged as a viable treatment option for repairing neurological disorders. However, the primarily limitations in the neuroregeneration field are uncontrolled cell differentiation, and low cell viability caused by the ischemic environment. The mechanical property of three-dimensional (3D) hydrogel can be easily controlled and shared similar characteristics with nerve tissue, thus promoting cell survival and controlled cell differentiation. We propose the combination of a 3D gelatin methacrylate (GelMA) hydrogel with iPSC-derived NSCs (iNSCs) to promote regeneration after SCI. In vitro, the iNSCs photoencapsulated in the 3D GelMA hydrogel survived and differentiated well, especially in lower-moduli hydrogels. More robust neurite outgrowth and more neuronal differentiation were detected in the soft hydrogel group. To further evaluate the in vivo neuronal regeneration effect of the GelMA hydrogels, a mouse spinal cord transection model was generated. We found that GelMA/iNSC implants significantly promoted functional recovery. Further histological analysis showed that the cavity areas were significantly reduced, and less collagen was deposited in the GelMA/iNSC group. Furthermore, the GelMA and iNSC combined transplantation decreased inflammation by reducing activated macrophages/microglia (CD68-positive cells). Additionally, GelMA/iNSC implantation showed striking therapeutic effects of inhibiting GFAP-positive cells and glial scar formation while simultaneously promoting axonal regeneration. Undoubtedly, use of this 3D hydrogel stem cell-loaded system is a promising therapeutic strategy for SCI repair.

Hydrogels, because of their water-rich nature and soft mechanical characteristics that resemble those of skin tissues, are promising materials for artificial skin. Existing piezoresistive hydrogels combine unique tissue-like and sensory properties, but these materials are often plagued by problems such as poor mechanical properties and the requirement of an external power supply or batteries. Here, a tough and self-powered hydrogel based on a tough polyacrylonitrile hydrogel incorporating ferroelectric poly(vinylidene fluoride) (PAN-PVDF) is reported. The dipolar interactions between the PVDF and PAN chains cause an increase in the best electroactive β-phase PVDF percentage in the composites from 0 to 91.3%; thus, a maximum piezoelectric coefficient d 33 , 30 pC N −1 , was achieved for the hydrogels. Skin-like Young's modulus values (1.33− 4.24 MPa), stretchability (90−175%), and high toughness (1.23 MJ/m 2 ) were achieved simultaneously for the hydrogels. This tough gel is capable of generating an electrical signal output (≈30 mV and ≈2.8 μA) with a rapid response (≈31 ms) due to the stress-induced poling effect. Moreover, the gel can also precisely detect physiological signals (e.g., gesture, pulse, and words). This study provides a simple and efficient method for artificial skin with high toughness, self-power generation capability, fast response, low cost, and tissue-like properties.