Artificial enzymes, especially nanozymes, have attracted wide attention due to their controlled catalytic activity, selectivity, and stability. The rising Cerium-based nanozymes exhibit unique SOD-like activity, and Vanadium-based nanozymes always hold excellent GPx-like activity. However, most inflammatory diseases involve polymerase biocatalytic processes that require multi-enzyme activities. The nanocomposite can fulfill multi-enzymatic activity simultaneously, but large nanoparticles (>10 nm) cannot be excreted rapidly, leading to biosafety challenges. Herein, atomically precise Ce12V6 clusters with a size of 2.19 nm are constructed. The Ce12V6 clusters show excellent glutathione peroxidase (GPx) -like activity with a significantly lower Michaelis-Menten constant (Km, 0.0125 mM versus 0.03 mM of natural counterpart) and good activities mimic superoxide dismutase (SOD) and peroxidase (POD). The Ce12V6 clusters exhibit the ability to scavenge the ROS including O2 ·- and H2O2 via the cascade reactions of multi-enzymatic activities. Further, the Ce12V6 clusters modulate the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and consequently rescue the multi-organ failure in the lipopolysaccharide (LPS)-induced sepsis mouse model. With excellent biocompatibility, the Ce12V6 clusters show promise in the treatment of sepsis.

Temporomandibular joint (TMJ) cartilage repair poses a considerable clinical challenge, and tissue engineering has emerged as a promising solution. In this study, we developed an injectable reactive oxygen species (ROS)-responsive multifunctional hydrogel (RDGel) to encapsulate dental pulp stem cells (DPSCs/RDGel in short) for the targeted repair of condylar cartilage defect. The DPSCs/RDGel composite exhibited a synergistic effect in the elimination of TMJ OA (osteoarthritis) inflammation via the interaction between the hydrogel component and the DPSCs. We first demonstrated the applicability and biocompatibility of RDGel. RDGel encapsulation could enhance the anti-apoptotic ability of DPSCs by inhibiting P38/P53 mitochondrial apoptotic signal in vitro. We also proved that the utilization of DPSCs/RDGel composite effectively enhanced the expression of TMJOA cartilage matrix and promoted subchondral bone structure in vivo. Subsequently, we observed the synergistic improvement of DPSCs/RDGel composite on the oxidative stress microenvironment of TMJOA and its regulation and promotion of M2 polarization, thereby confirmed that M2 macrophages further promoted the condylar cartilage repair of DPSCs. This is the first time application of DPSCs/RDGel composite for the targeted repair of TMJOA condylar cartilage defects, presenting a novel and promising avenue for cell-based therapy.

Neutrophil extracellular traps (NETs) seriously impede diabetic wound healing. The disruption or scavenging of NETs using deoxyribonuclease (DNase) or cationic nanoparticles has been limited by liberating trapped bacteria, short half-life, or potential cytotoxicity. In this study, a positive correlation between the NETs level in diabetic wound exudation and the severity of wound inflammation in diabetic patients is established. Novel NETs scavenging bio-based hydrogel microspheres \'micro-cage\', termed mPDA-PEI@GelMA, is engineered by integrating methylacrylyl gelatin (GelMA) hydrogel microspheres with cationic polyethyleneimine (PEI)-functionalized mesoporous polydopamine (mPDA). This unique \'micro-cage\' construct is designed to non-contact scavenge of NETs between nanoparticles and the diabetic wound surface, minimizing biological toxicity and ensuring high biosafety. NETs are introduced into \'micro-cage\' along with wound exudation, and cationic mPDA-PEI immobilizes them inside the \'micro-cage\' through a strong binding affinity to the cfDNA web structure. The findings demonstrate that mPDA-PEI@GelMA effectively mitigates pro-inflammatory responses associated with diabetic wounds by scavenging NETs both in vivo and in vitro. This work introduces a novel nanoparticle non-contact NETs scavenging strategy to enhance diabetic wound healing processes, with potential benefits in clinical applications.

The development of numerous diseases is significantly influenced by inflammation. Macrophage-derived exosomes (M-Exos) play a role in controlling inflammatory reactions in various conditions, including chronic inflammatory pain, hypertension, and diabetes. However, the specific targets and roles of M-Exos in regulating inflammation in diseases remain largely unknown. This review summarizes current knowledge on M-Exos biogenesis and provides updated information on M-Exos\' biological function in inflammation modulation. Furthermore, this review highlights the functionalization and engineering strategies of M-Exos, while providing an overview of cutting-edge approaches to engineering M-Exos and advancements in their application as therapeutics for inflammation modulation. Finally, multiple engineering strategies and mechanisms are presented in this review along with their perspectives and challenges, and the potential contribution that M-Exos may have in diseases through the modulation of inflammation is discussed.

The intricate relationship between resistant starch (RS) and the gut microbiome presents a dynamic frontier in nutrition science. This review synthesizes current understandings of how RS, an indigestible form of starch found naturally in certain foods and also enhanced through various modification methods, interacts with the gut microbiome. We particularly focus on how RS fermentation in the colon contributes to the production of beneficial volatile fatty acids (VFAs) such as butyrate, acetate, and propionate. These VFAs have been recognized for their vital roles in maintaining gut barrier integrity, modulating inflammation, and potentially influencing systemic health. Additionally, we discuss the dietary implications of consuming foods rich in RS, both in terms of gut health and broader metabolic outcomes. By consolidating these insights, we emphasize the significance of RS in the context of dietary strategies aimed at harnessing the gut microbiome\'s potential to impact human health.

Dendrobium officinale polysaccharides (DOPs) are important active polysaccharides found in Dendrobium officinale, which is commonly used as a conventional food or herbal medicine and is well known in China. DOPs can influence the composition of the gut microbiota and the degradation capacity of these symbiotic bacteria, which in turn may determine the efficacy of dietary interventions. However, the necessary analysis of the relationship between DOPs and the gut microbiota is lacking. In this review, we summarize the extraction, structure, health benefits, and related mechanisms of DOPs, construct the DOPs-host axis, and propose that DOPs are potential prebiotics, mainly composed of 1,4-β-D-mannose, 1,4-β-D-glucose, and O-acetate groups, which induce an increase in the abundance of gut microbiota such as Lactobacillus, Bifidobacterium, Akkermansia, Bacteroides, and Prevotella. In addition, we found that when exposed to DOPs with different structural properties, the gut microbiota may exhibit different diversity and composition and provide health benefits, such as metabolism regulations, inflammation modulation, immunity moderation, and cancer intervention. This may contribute to facilitating the development of functional foods and health products to improve human health.

Trauma and its associated complications, including dysregulated inflammatory responses, severe infection, and disseminated intravascular coagulation (DIC), continue to pose lethal threats worldwide. Following injury, cell-free nucleic acids (cfNAs), categorized as damage-associated molecular patterns (DAMPs), are released from dying or dead cells, triggering local and systemic inflammatory responses and coagulation abnormalities that worsen disease progression. Harnessing cfNA scavenging strategies with biomaterials has emerged as a promising approach for treating posttrauma systemic inflammation. In this study, the effectiveness of cationic hyperbranched polyaminoglycosides derived from tobramycin (HPT) and disulfide-included HPT (ss-HPT) in scavenging cfNAs to mitigate posttrauma inflammation and hypercoagulation is investigated. Both cationic polymers demonstrate the ability to suppress DAMP-induced toll-like receptor (TLR) activation, inflammatory cytokine secretion, and hypercoagulation by efficiently scavenging cfNAs. Additionally, HPT and ss-HPT exhibit potent antibacterial efficacy attributed to the presence of tobramycin in their chemical composition. Furthermore, HPT and ss-HPT exhibit favorable modulatory effects on inflammation and therapeutic outcomes in a cecal ligation puncture (CLP) mouse abdominal trauma model. Notably, in vivo studies reveal that ss-HPT displayed high accumulation and retention in injured organs of traumatized mice while maintaining a higher biodegradation rate in healthy mice, contrasting with findings for HPT. Thus, functionalized ss-HPT, a bioreducible polyaminoglycoside, holds promise as an effective option to enhance therapeutic outcomes for trauma patients by alleviating posttrauma inflammation and coagulation complications.

We investigated the inflammatory (IL-1 alpha) and thermal (infrared thermography) reactions of healthy sacral skin to sustained, irritating mechanical loading. We further acquired digital photographs of the irritated skin (at the visible light domain) to assess whether infrared imaging is advantageous. For clinical context, the skin status was monitored under a polymeric membrane dressing known to modulate the inflammatory skin response. The IL-1 alpha and infrared thermography measurements were consistent in representing the skin status after 40 min of continuous irritation. Infrared thermography overpowered conventional digital photography as a contactless optical method for image processing inputs, by revealing skin irritation trends that were undetectable through digital photography in the visual light, not even with the aid of advanced image processing. The polymeric membrane dressings were shown to offer prophylactic benefits over simple polyurethane foam in the aspects of inflammation reduction and microclimate management. We also concluded that infrared thermography is a feasible method for monitoring the skin health status and the risk for pressure ulcers, as it avoids the complexity of biological marker studies and empowers visual skin assessments or digital photography of skin, both of which were shown to be insufficient for detecting the inflammatory skin status.

Diabetic wound treatment faces great challenges in clinic. Staphylococcus aureus (S. aureus) is one of the most frequently isolated pathogens from the diabetic infections, which can severely impede wound healing time. Herein, ferrous sulfide (FeS) nanoparticles were fabricated through an in situ reaction between Fe2+ and S2- in glycyrrhizic acid (GA) solution. As the FeS nanoparticles aged, the solution gradually transformed into a gel, exhibiting excellent mechanical strength, injectability, and biocompatibility as a wound dressing. In addition to its own pharmacological effects, GA could act as the protector for FeS from oxidation of air. It also provided a weak acidic microenvironment, facilitating the pH-dependent dissolution reaction of FeS to release H2S and Fe2+. Notably, the effective antibacterial performance of the FeS/GA hydrogels towards S. aureus and multi-drug resistant S. aureus (MRSA) was achieved via the degradedly released Fe2+ and H2S through combination of ferroptosis damage and energy metabolism disruption. Moreover, FeS/GA hydrogels effectively modulated the proportion of M1/M2 macrophages, reduced the secretion of inflammatory cytokines, and significantly enhanced the proliferation and migration of fibroblasts in vitro. Importantly, in an MRSA-infected diabetic wound model, the FeS/GA hydrogels efficiently eradicated bacteria and regulated the inflammatory microenvironment, thereby promoting the diabetic wound repair. Overall, our study establishes a novel strategy for developing multifunctional hydrogels that serve as an effective therapeutic platform for managing bacteria-infected diabetic wounds.

Cutaneous wound healing is a complex process that leads the skin reparation with the formation of scar tissue that typically lacks skin appendages. This fact drives us to find new strategies to improve regenerative healing of the skin. This study outlines, the contribution of colloidal silica particles and oligourethane crosslinking on the collagen material properties and the effect on skin wound healing in rats. We characterized the gel properties that are key forin-situgelation, which is accomplished by the latent reactivity of oligourethane bearing blocked isocyanate groups to crosslink collagen while entrapping silica particles. The swelling/degradation behavior and the elastic modulus of the composite gel were consistent with the modification of collagen type I with oligourethane and silica. On the other hand, these gels were characterized as scaffold for murine macrophages and human stem cells. The application of a composite gel dressing on cutaneous wounds showed a histological appearance of the recovered skin as intact skin; featured by the epidermis, hair follicles, sebaceous glands, subcutaneous adipose layer, and dermis. The results suggest that the collagen-based composite dressings are promising modulators in skin wound healing to achieve a regenerative skin closure with satisfactory functional and aesthetic scars.