A Biomimetic Autophagosomes-Based Nanovaccine Boosts Anticancer Immunity.

Personalized cancer vaccines based on tumor cell lysates offer promise for cancer immunotherapy yet fail to elicit a robust therapeutic effect due to the weak immunogenicity of tumor antigens. Autophagosomes, obtained from pleural effusions and ascites of cancer patients, have been identified as abundant reservoirs of tumor neoantigens that exhibit heightened immunogenicity. However, their potential as personalized cancer vaccines have been constrained by suboptimal lymphatic-targeting performances and challenges in antigen-presenting cell endocytosis. Here,a reinforced biomimetic autophagosome-based (BAPs) nanovaccine generated by precisely amalgamating autophagosome-derived neoantigens and two types of adjuvants capable of targeting lymph nodes is developed to potently elicit antitumor immunity. The redox-responsive BAPs facilitate cytosolic vaccine opening within antigen-presenting cells, thereby exposing adjuvants and antigens to stimulate a strong immune response. BAPs evoke broad-spectrum T-cell responses, culminating in the effective eradication of 71.4% of established tumors. Notably, BAPs vaccination triggers enduring T-cell responses that confer robust protection, with 100% of mice shielded against tumor rechallenge and a significant reduction in tumor incidence by 87.5%. Furthermore, BAPs synergize with checkpoint blockade therapy to inhibit tumor growth in the poorly immunogenic breast cancer model. The biomimetic approach presents a powerful nanovaccine formula with high versatility for personalized cancer immunotherapy.

Deciphering the crop-soil-enzyme C:N:P stoichiometry nexus: A 5-year study on manure-induced changes in soil phosphorus transformation and release risk.

Carbon:nitrogen:phosphorus (C:N:P) stoichiometry plays a vital role in regulating P transformation in agriculture ecosystems. However, the impact of balanced C:N:P stoichiometry in paddy soil, particularly regarding relative soil P transformation, remains unknown. This study explores the response of C:N:P stoichiometry to manure substitution and its regulatory role in soil P transformation, along with the associated release risk to the environment. Based on a 5-year field study, our findings reveal that replacing 30 % of chemical P fertilizer with pig manure (equal total NPK amounts with chemical P fertilizer treatment, named CFM) increased soil total C without altering soil total P, resulting in an elevated soil C:P ratio, despite the homeostasis of crop stoichiometry. This increase promoted microbial diversity and the accumulation of organic P in the soil. The Proteobacteria and Actinobacteria produced lower C:PEEA metabolism together, and enhanced in vivo turnover of P. Additionally, by integrating high-resolution dialysis (HR-Peeper), diffusive gradients in thin films (DGT), DGT-induced fluxes in the soil (DIFS), and sediment P release risk index (SPRRI) models, we observed that, in addition to organic P, CFM simultaneously increased soil Al-P, thereby weakening the diffusion and resupply capacity of P from soil solids to the solution. Consequently, this decrease in P release risk to the environment was demonstrated. Overall, this study establishes a connection between crop-soil-enzyme C:N:P stoichiometry, soil microorganisms, and soil P biogeochemical processes. The study further evaluates the P release risk to the environment, providing a novel perspective on both the direct and indirect effects of manure substitution on soil P cycling.

BI-FedGNN: Federated graph neural networks framework based on Bayesian inference.

The development of the Industrial Internet of Things (IIoT) in recent years has resulted in an increase in the amount of data generated by connected devices, creating new opportunities to enhance the quality of service for machine learning in the IIoT through data sharing. Graph neural networks (GNNs) are the most popular technique in machine learning at the moment because they can learn extremely precise node representations from graph-structured data. Due to privacy issues and legal restrictions of clients in industrial IoT, it is not permissible to directly concentrate vast real-world graph-structured datasets for training on GNNs. To resolve the aforementioned difficulties, this paper proposes a federal graph learning framework based on Bayesian inference (BI-FedGNN) that performs effectively in the presence of noisy graph structure information or missing strong relational edges. BI-FedGNN extends Bayesian Inference (BI) to the process of Federal Graph Learning (FGL), adding random samples with weights and biases to the client-side local model training process, improving the accuracy and generalization ability of FGL in the training process by rendering the graph structure data involved in GNNs training more similar to the graph structure data existing in the real world. Through extensive experimental tests, the results show that BI-FedGNN has about 0.5%-5.0% accuracy improvement over other baselines of federal graph learning. In order to expand the applicability of BI-FedGNN, experiments are carried out on heterogeneous graph datasets, and the results indicate that BI-FedGNN can also have at least 1.4% improvement in classification accuracy.

An in situ dual-anchoring strategy for enhanced immobilization of PD-L1 to treat autoimmune diseases.

Immune checkpoints play key roles in maintaining self-tolerance. Targeted potentiation of the checkpoint molecule PD-L1 through in situ manipulation offers clinical promise for patients with autoimmune diseases. However, the therapeutic effects of these approaches are often compromised by limited specificity and inadequate expression. Here, we report a two-step dual-anchor coupling strategy for enhanced immobilization of PD-L1 on target endogenous cells by integrating bioorthogonal chemistry and physical insertion of the cell membrane. In both type 1 diabetes and rheumatoid arthritis mouse models, we demonstrate that this approach leads to elevated and sustained conjugation of PD-L1 on target cells, resulting in significant suppression of autoreactive immune cell activation, recruitment of regulatory T cells, and systematic reshaping of the immune environment. Furthermore, it restores glucose homeostasis in type 1 diabetic mice for over 100 days. This specific in situ bioengineering approach potentiates the functions of PD-L1 and represents its translational potential.

Scarless wound healing programmed by core-shell microneedles.

Effective reprogramming of chronic wound healing remains challenging due to the limited drug delivery efficacy hindered by physiological barriers, as well as the inappropriate dosing timing in distinct healing stages. Herein, a core-shell structured microneedle array patch with programmed functions (PF-MNs) is designed to dynamically modulate the wound immune microenvironment according to the varied healing phases. Specifically, PF-MNs combat multidrug-resistant bacterial biofilm at the early stage via generating reactive oxygen species (ROS) under laser irradiation. Subsequently, the ROS-sensitive MN shell gradually degrades to expose the MN core component, which neutralizes various inflammatory factors and promotes the phase transition from inflammation to proliferation. In addition, the released verteporfin inhibits scar formation by blocking Engrailed-1 (En1) activation in fibroblasts. Our experiments demonstrate that PF-MNs promote scarless wound repair in mouse models of both acute and chronic wounds, and inhibit the formation of hypertrophic scar in rabbit ear models.

Adoptive Treg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome.

Regulatory T (Treg) cells underlie multiple autoimmune disorders and potentialize an anti-inflammation treatment with adoptive cell therapy. However, systemic delivery of cellular therapeutics often lacks tissue targeting and accumulation for localized autoimmune diseases. Besides, the instability and plasticity of Treg cells also induce phenotype transition and functional loss, impeding clinical translation. Here, we developed a perforated microneedle (PMN) with favorable mechanical performance and a spacious encapsulation cavity to support cell survival, as well as tunable channels to facilitate cell migration for local Treg therapy of psoriasis. In addition, the enzyme-degradable microneedle matrix could release fatty acid in the hyperinflammatory area of psoriasis, enhancing the Treg suppressive functions via the fatty acid oxidation (FAO)-mediated metabolic intervention. Treg cells administered through PMN substantially ameliorated psoriasis syndrome with the assistance of fatty acid-mediated metabolic intervention in a psoriasis mouse model. This tailorable PMN could offer a transformative platform for local cell therapy to treat a variety of diseases.

Legume cover with optimal nitrogen management and nitrification inhibitor enhanced net ecosystem economic benefits of peach orchard.

Peach (Prunus persica L.), as a traditional kind of fruits in China, was extremely dependent on large application of nitrogen (N) fertilizer to maintain high fruit yield and commercial income, resulting in raising environmental damage risk. Therefore, a three-year field trail was conducted to clarify the environmental N loss under conventional management, investigate the positive effects of optimal N management, legume cover and 3,4-dimethylpyrazole phosphate (DMPP) on N input/output and the net ecosystem economic benefits (NEEB). There are four treatments in this study: conventional fertilizer management with 521.1 kg N ha-1 yr-1 input (CU); optimal N management including 406.4 kg N ha-1 yr-1 input and deep fertilization (OP); DMPP was added to OP at rate of 1 % (w/w) (OPD); legume (white clover) was covered to OPD (OPDG). Results showed 102.9 kg N ha-1 was removed by annual fruit and residues (including pruned branches, pruned and fallen leaves), while 70.2 kg N ha-1 was lost to the environment by ammonia (NH3), nitrous oxide (N2O) and N runoff loss under the conventional fertilizer management. While, the optimal N management mitigated NH3 volatilization about 49.3 %, further added DMPP abated N2O emission by 61.4 %, besides covered white clover lowered N runoff loss by 64.5 %. The NEEB results revealed that optimal N management combined with added DMPP and covered white clover could minimize the production cost, reduce environmental damage cost by 35.9 %, increase fruit yield by 10.3 % and achieved the maximum NEEB with improvement of 27.1 %, in comparison of the conventional fertilizer management. Generally, conventional peach cultivation constituted overwhelming N loss to raise potential environmental risk. While, extending mode of optimized N management combined with DMPP and legume cover could not only realize high fruit revenue, but also abate environmental N losses, thereby should be considered as effective strategy for sustainable fruit cropping systems.

Ceria Nanoenzyme-Based Hydrogel with Antiglycative and Antioxidative Performance for Infected Diabetic Wound Healing.

Diabetic wound healing still faces a dilemma because of the hostile hyperglycemic, oxidative, and easily-infected wound microenvironment. In addition, advanced glycation end products (AGEs) further impede wound repair by altering the immunological balance. Herein, ceria nanorods with distinctive antiglycative and excellent antioxidative capacities are innovatively introduced into a self-healing and erasable hydrogel, which could reshape the wound microenvironment by expediting hemostasis, inhibiting infection, reducing AGEs, and continuously depleting reactive oxygen species. The remitted oxidative stress and glycosylation synergistically regulate inflammatory responses, and promote revascularization and extracellular matrix deposition, resulting in accelerated diabetic wound repair. This study provides a highly efficient strategy for constructing nanoenzyme-reinforced antiglycative hydrogel that regulates every wound healing stage for diabetic wound management.

Advances in Translational 3D Printing for Cartilage, Bone, and Osteochondral Tissue Engineering.

The regeneration of 3D tissue constructs with clinically relevant sizes, structures, and hierarchical organizations for translational tissue engineering remains challenging. 3D printing, an additive manufacturing technique, has revolutionized the field of tissue engineering by fabricating biomimetic tissue constructs with precisely controlled composition, spatial distribution, and architecture that can replicate both biological and functional native tissues. Therefore, 3D printing is gaining increasing attention as a viable option to advance personalized therapy for various diseases by regenerating the desired tissues. This review outlines the recently developed 3D printing techniques for clinical translation and specifically summarizes the applications of these approaches for the regeneration of cartilage, bone, and osteochondral tissues. The current challenges and future perspectives of 3D printing technology are also discussed.

Injectable hybrid inorganic nanoscaffold as rapid stem cell assembly template for cartilage repair.

Cartilage injuries are often devastating and most cannot be cured because of the intrinsically low regenerative capacity of cartilage tissues. Although stem-cell therapy has shown enormous potential for cartilage repair, the therapeutic outcome has been restricted by low survival rates and poor chondrocyte differentiation in vivo. Here, we report an injectable hybrid inorganic (IHI) nanoscaffold that facilitates fast assembly, enhances survival and regulates chondrogenic differentiation of stem cells. IHI nanoscaffolds that strongly bind to extracellular matrix (ECM) proteins assemble stem cells through synergistic 3D cell-cell and cell-matrix interactions, creating a favorable physical microenvironment for stem-cell survival and differentiation in vitro and in vivo. Additionally, chondrogenic factors can be loaded into nanoscaffolds with a high capacity, which allows deep, homogenous drug delivery into assembled 3D stem-cell-derived tissues for effective control over the soluble microenvironment of stem cells. The developed IHI nanoscaffolds that assemble with stem cells are injectable. They also scavenge reactive oxygen species and timely biodegrade for proper integration into injured cartilage tissues. Implantation of stem-cell-assembled IHI nanoscaffolds into injured cartilage results in accelerated tissue regeneration and functional recovery. By establishing our IHI nanoscaffold-templated 3D stem-cell assembly method, we provide a promising approach to better overcoming the inhibitory microenvironment associated with cartilage injuries and to advance current stem-cell-based tissue engineering.

Animal manures promoted soil phosphorus transformation via affecting soil microbial community in paddy soil.

Animal manures are reported as good substitutes for chemical fertilizers to mobilize soil phosphorus (P). However, the mechanisms on how different types of manures regulate microbial biomass involved in P mobilization remain unclear. In this study, we conducted a two-year field experiment to investigate variations in soil microbial biomass carbon (MBC) and P (MBP) and P fractions after 30% animal manures substitution (pig manure (PM), chicken manure (CM), and dairy manure (DM)) in paddy soil. Furthermore, a 30-day incubation experiment was used to explore the mechanisms of soil P transformation induced by 100% manures addition. Two-year field experiment results showed that, compared to the chemical NPK fertilizer, 30% manure substitution didn't influence rice and wheat yields significantly but decreased soil total P loss from runoff by 3.2%. However, 30% manure substitution significantly enhanced MBC and MBP by 11.3-18.4% and 57.1-81.2%, respectively, which also promoted the transformation of moderately labile P (M-P) to labile P (L-P). Moreover, the incubation experiment also convinced that all manures caused higher MBC than chemical P fertilizer. Meanwhile, compared to the no P fertilizer, manures increased L-P and organic P by 2.7%-14.7% and 6.4%-20.0%, respectively. Redundancy analysis indicated that soil MBC/MBP ratio was the main factor to soil L-P and M-P, indicating that animal manures can improve soil microbial abundance and thus promote M-P to L-P in soil. Among three animal manures, PM could improve the mobilization potential of P mostly, due to the highest C source activity by 13C NMR analysis. Our study indicated that animal manures especially PM can be considered as a good candidate for agricultural P management in paddy soils because of their capacity to promote soil P transformation.

Biochar mitigated more N-related global warming potential in rice season than that in wheat season: An investigation from ten-year biochar-amended rice-wheat cropping system of China.

Rice-wheat cropping system (RWCS), the major rice-based cropping system, constitutes a significant source of N-related greenhouse gas (GHG) emission due to the unique wet-dry alternation process. Biochar is often highlighted as a potential solution for reducing fertilizer N losses, hence, understanding its effects on Ngr emissions (mainly NH3 and N2O) under wet-dry conditions is critical to inform strategies for GHG mitigation. This study investigated the responses of NH3 and N2O emissions to biochar amendments during rice and wheat seasons based on in situ measurements under ten-year successive straw biochar application in RWCS. Our results indicated that 43.7% and 89.9% of N2O and NH3 emissions were emitted during rice season and 56.3% and 10.1% during wheat season, respectively. Long-term biochar amendment was found to play significant role in mitigating NH3 emissions (38.6-43.9%), which could be attributed to the disappearance of liming effect of aged-biochar on flooding water and decreased NH4+ concentrations in the soil. However, considerable variation of N2O emissions were observed in RWCS. Biochar showed a significant decreasing effect on the net global warming potential related to N2O and NH3 emissions (GWPN) in rice season (16.1-89.6%), and slight increased tendency in wheat season (1.43-13.1%) primarily due to its positive effects on N2O emission. Biochar amendment mainly BC22.5, significantly increased above-ground yields by 9.22% in rice season. Thus, it is a low carbon-producing and sustainable crop management method that can support crop production, C sequestration, and GHG mitigation in rice season under RWCS from the viewpoint of the Ngr mitigation. Our results suggest that emission patterns of N2O and NH3 varied with wet-dry alternation under the disturbance of long-term biochar amendment in RWCS; moreover, long-term biochar application exhibited significant potential for mitigating soil Ngr losses in rice season for RWCS.

Cu-doped cerium oxide-based nanomedicine for tumor microenvironment-stimulative chemo-chemodynamic therapy with minimal side effects.

CeO2 nanoenzyme possesses multiple enzyme-mimicking activities and excellent biocompatibility. However, its weak peroxidase (POD)-mimicking property in the tumor microenvironment (TME) hinders its further tumor therapy application. To enhance CeO2 nanoenzyme's POD activity and overcome limitations of single therapeutic modality, a novel antitumor controlled drug release system (CCCs NPs) was designed using Cu doped cerium oxide nanoparticles (Cu-CeO2 NPs) loaded with clinical anti-cancer drug doxorubicin (DOX) as the core and the breast cancer cell membrane as the outer shell. Cu doping endowed CeO2 NPs' with significantly enhanced POD-mimicking activity in the TME due to a remarkably higher Ce3+/Ce4+ ratio. The cancer cell membrane coating enabled our nanomedicine with homotypic targeting property. Combined with chemotherapeutic drug DOX, a selective and nearly complete tumor suppression was demonstrated in vitro and in vivo. Remarkably, under physiological condition, CCCs NPs worked as a radical scavenger to protect normal cells from oxidative stress caused by anti-cancer drug DOX and OH generated via Fenton-like reaction. Collectively, our CCCs NPs offered a therapeutic potential for effective breast cancer therapy while being free of side effects.

Characterization of Different Phosphorus Forms in Flooded and Upland Paddy Soils Incubated with Various Manures.

Phosphorus (P) is an essential nutrient for crop production, and animal manures are rich in P. When using animal manures as alternatives to synthetic fertilizers, it is important to know the kinetics of P release from different animal manures and the forms, amounts, and dynamics of P in manure-treated soils. We chose four types of manure, viz., pig manure (PM), chicken manure (CM), dairy manure (DM), and commercial organic compost (OM), and evaluated the P release rate and availability in water solution and flooded/upland paddy soils. The WEP/total P (TP) and the water-extractable P (WEP) concentrations are highest for OM with the order: OM > PM > CM > DM. An increase in soil Olsen-P concentration was observed for the addition of manure with a varying application rate of P from low to moderate to high. The release capacity of Olsen-P in flooded conditions was higher than that in upland conditions. Under the flooded soil, PM and OM have faster release rates than CM and OM in the upland soil. Moreover, PM significantly increased available P by 29% in the flooded paddy soil while moderately inorganic P increased by 17% in the upland paddy soil. Olsen-P has a significant linear relationship with available P (Resin-P + NaHCO3-Pi; R 2 = 0.104; P < 0.01) and moderately inorganic P (NaOH-Pi + HCl-P; R 2 = 0.286; P < 0.01). The structural equation model showed that the organic input was beneficial to the conversion of moderately inorganic P to available P. Our results indicate that PM amendment promotes the release of available P in paddy soil.

Conductive Antibacterial Hemostatic Multifunctional Scaffolds Based on Ti3C2Tx MXene Nanosheets for Promoting Multidrug-Resistant Bacteria-Infected Wound Healing.

Chronic bacterial-infected wound healing/skin regeneration remains a challenge due to drug resistance and the poor quality of wound repair. The ideal strategy is combating bacterial infection, while facilitating satisfactory wound healing. However, the reported strategy hardly achieves these two goals simultaneously without the help of antibiotics or bioactive molecules. In this work, a two-dimensional (2D) Ti3C2Tx MXene with excellent conductivity, biocompatibility, and antibacterial ability was applied in developing multifunctional scaffolds (HPEM) for methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing. HPEM scaffolds were fabricated by the reaction between the poly(glycerol-ethylenimine), Ti3C2Tx MXene@polydopamine (MXene@PDA) nanosheets, and oxidized hyaluronic acid (HCHO). HPEM scaffolds presented multifunctional properties containing self-healing behavior, electrical conductivity, tissue-adhesive feature, antibacterial activity especially for MRSA resistant to many commonly used antibiotics (antibacterial efficiency was 99.03%), and rapid hemostatic capability. HPEM scaffolds enhanced the proliferation of normal skin cells with negligible toxicity. Additionally, HPEM scaffolds obviously accelerated the MRSA-infected wound healing (wound closure ratio was 96.31%) by efficient anti-inflammation effects, promoting cell proliferation, and the angiogenic process, stimulating granulation tissue formation, collagen deposition, vascular endothelial differentiation, and angiogenesis. This study indicates the important role of multifunctional 2D MXene@PDA nanosheets in infected wound healing. HPEM scaffolds with multifunctional properties provide a potential strategy for MRSA-infected wound healing/skin regeneration.

Biomimetic Brushlike Slippery Coatings with Mechanically Robust, Self-Cleaning, and Icephobic Properties.

In this work, a facile strategy was proposed to prepare a series of brushlike thermoplastic polyurethane (TPU) coatings with mechanically robust, self-cleaning, and icephobic performance. Through a simple multicomponent click reaction of thiolactone with a diamine compound and mono-ethenyl-terminated polydimethylsiloxane (mono-ethenyl-PDMS), a diol with amide groups and flexible PDMS was synthesized, and a novel TPU could be obtained productively by a reaction of isocyanate and diol. The unique chain structure endowed TPU films with ascendant self-stratifying properties. During solvent vapor annealing, flexible PDMS chains migrated and enriched to the surface while urethane linkages with a strong interaction tended to locate at the substrate. Based on this, TPU-PDMS films exhibited mechanically robust property, and the tensile strength value of TPU-PDMS-3 showed a sharp increase to 48.62 MPa. The resultant TPU-PDMS-10 coatings exhibited a water repellent behavior and possessed superior movability of droplet water, and also the dirt on it could be readily removed by rinsing with water without leaving any traces. Furthermore, three different criteria were used to characterize the icephobic performance. The coatings exhibited a significantly lower freezing point (approximately -27 °C) of supercooled water, longer delay-icing time, and less ice adhesion shear strength. Therefore, these novel brushlike TPU coatings have tremendous potential applications.

Structural and microbial evidence for different soil carbon sequestration after four-year successive biochar application in two different paddy soils.

Application of biochar (BC) derived from rice straw has generated increasing interest in long-term storage of soil organic carbon (SOC), however its carbon (C) sequestration potential vary widely among agricultural soils despite the same BC dose used. These discrepancies in the ability of soils to sequester C after BC application are poorly understood. Metabolic quotient (qCO2) is a reflection of "microbial efficiency" and linked to SOC turnover across ecosystems. Therefore, we investigated the SOC sequestration and qCO2 in a Yellow River alluvium paddy soil (YP) and a quaternary red clay paddy soil (QP) under rice-wheat annual rotation following 4-year of BC application rate of 11.3 Mg ha-1 per cropping season. BC application consistently brought 65.3 Mg C ha-1 into the soils over 4-year experimental period but increased SOC by 57.6 Mg C ha-1 in YP and 64.5 Mg C ha-1 in QP. Calculating SOC mass balance showed 11.7% of BC-C losses from YP and only 1.16% from QP. BC application stimulated the G+ bacterial, fungi, and actinomycetes by increasing O-alkyl C content in YP, while decreased the same microorganisms by decreasing anomeric C-H content in QP. Importantly, higher clay and amorphous Fe (Feo) contents in QP after BC application protected SOC from further decomposition, which in turn decreased microorganisms and resulted in higher SOC sequestration than YP. Our results indicated that soil properties controlled the extent of SOC sequestration after BC application and site-specific soil properties must be carefully considered to maximize long-term SOC sequestration after BC application.

Biodegradable conductive multifunctional branched poly(glycerol-amino acid)-based scaffolds for tumor/infection-impaired skin multimodal therapy.

The tumor/infection-impaired skin regeneration is still a challenge and the single modal therapy strategy is usually inefficient. Herein, a multimodal tumor therapy and antiinfection method based on the conductive multifunctional poly(glycerol-amino acid)-based scaffolds is reported. The multifunctional conductive scaffolds were formed through the crosslinking between branched poly(glycerol-amino acid), polypyrrole@polydopamine (PPy@PDA) nanoparticles and aldehyde F127 (PGFP scaffolds). PGFP scaffolds possessed controlled electrical conductivity, skin-adhesive behavior, broad-spectrum antibacterial activity, photothermal-responsive drug release and good cytocompatibility. Thus, PGFP scaffolds demonstrated the significant photothermo-chemo tumor and multidrug resistant infection therapy in vitro and in vivo, while promoting granulation tissue formation, collagen deposition, vascular endothelial differentiation and accelerated skin regeneration. This work also firstly demonstrated the important role of multifunctional conductive PPy@PDA nanoparticles in tumor/infection-impaired skin multimodal therapy. This study suggests that efficient multimodal therapy on diseased-impaired skin could be achieved through optimizing the structure and multifunctional properties of biomaterials.

Effective Modulation of CNS Inhibitory Microenvironment using Bioinspired Hybrid-Nanoscaffold-Based Therapeutic Interventions.

Central nervous system (CNS) injuries are often debilitating, and most currently have no cure. This is due to the formation of a neuroinhibitory microenvironment at injury sites, which includes neuroinflammatory signaling and non-permissive extracellular matrix (ECM) components. To address this challenge, a viscous interfacial self-assembly approach, to generate a bioinspired hybrid 3D porous nanoscaffold platform for delivering anti-inflammatory molecules and establish a favorable 3D-ECM environment for the effective suppression of the neuroinhibitory microenvironment, is developed. By tailoring the structural and biochemical properties of the 3D porous nanoscaffold, enhanced axonal growth from the dual-targeting therapeutic strategy in a human induced pluripotent stem cell (hiPSC)-based in vitro model of neuroinflammation is demonstrated. Moreover, nanoscaffold-based approaches promote significant axonal growth and functional recovery in vivo in a spinal cord injury model through a unique mechanism of anti-inflammation-based fibrotic scar reduction. Given the critical role of neuroinflammation and ECM microenvironments in neuroinhibitory signaling, the developed nanobiomaterial-based therapeutic intervention may pave a new road for treating CNS injuries.

Injectable redox and light responsive MnO2 hybrid hydrogel for simultaneous melanoma therapy and multidrug-resistant bacteria-infected wound healing.

The recurrence of cutaneous cancer and multidrug-resistant (MDR) bacteria infected-wound healing after surgical excision remains a great challenge for both clinic and research. In this study, we developed an injectable redox and light responsive bio-inspired MnO2 hybrid (BMH) hydrogel for effective melanoma photothermo-chemotherapy and MDR bacteria infected-wound healing. The BMH hydrogel was ingeniously fabricated via non-covalent self-assembly and MnO2 nanosheets mediated covalent oxidative polymerization of the catechol functionalized chitosan for the first time. The BMH hydrogel displayed excellent shear-thinning, injectable, adhesive, redox/light responsive and contact-active antibacterial capabilities. Remarkably, our rationally designed BMH hydrogel could alleviate the hypoxic tumor microenvironment (TME) by decomposing the endogenous H2O2 into O2, and simultaneously release anticancer drug DOX. Increasing the local availability of O2 enhanced the cytotoxicity of DOX against melanoma in a highly site-specific manner. By further combining with a spatiotemporal controllable photothermal hyperthermia, we demonstrated a near-complete tumor suppression both in vitro (98.6%) and large solid tumors in vivo (96.2%). Moreover, BMH hydrogel could significantly promote the MDR-infected wound healing in vivo by efficiently eradicating bacterial invasion and perpetually ameliorating the oxidative and inflammatory wound microenvironment. Collectively, BMH hydrogel indicated great therapeutic potentials for both cancer therapy and tissue engineering.