Synthetic biodegradable microspheres hold great promise for complex wound repair. However, their clinical application is hindered by inflammatory responses triggered by acidic degradation byproducts. In this paper, we developed new composite microspheres as dressings to accelerate infected wound healing. Polyethylene glycol/poly(L-lactide)/poly(ε-caprolactone) multiblock copolymers were synthesized and engineered with Cu-doped bioactive glass to form composite microspheres. The Cu-doped bioactive glass not only improved the hydrophilicity of the composite microspheres but also neutralized the acidic degradation products of the copolymers. This helped preserve a physiologically neutral pH in wounds, thereby attenuating inflammatory stimulation and fostering a stabilized microenvironment supportive of efficient wound healing. Simultaneously, the Cu2+ ions within the bioactive glass network were released gradually over 24 h to maintain sustained antibacterial activity and promote wound regeneration. Animal experiments demonstrated that the composite microspheres significantly accelerated the healing of wounds infected with Staphylococcus aureus. These composite microspheres represent a feasible solution for infected wound healing.

Natural bioactive compounds exhibit significant antioxidant and anti-inflammatory activities, offering a promising natural alternative or complement to current immunosuppressive therapies for ulcerative colitis (UC). However, achieving effective colon-targeted delivery of these compounds remains a significant challenge due to premature drug release and limited local retention. In this study, we present a nanoparticle-hydrogel composite system, BZH@HCE, designed to enhance the therapeutic efficacy of baicalein (BA) for UC treatment. Zein and oxidized hyaluronic acid-based nanoparticles (BZH) provide a high loading capacity for BA and prevent premature drug release in the upper gastrointestinal tract. BZH encapsulation within an epigallocatechin gallate (EGCG)-containing hydrogel matrix (HCE) further sustains BA release and amplifies its antioxidant and anti-inflammatory effects through synergistic action with EGCG. The adhesive hydrogel matrix ensures prolonged colon retention for up to 24 hours in colitis mice. In vivo studies using a dextran sulfate sodium-induced murine colitis model demonstrate that BZH@HCE significantly alleviates intestinal inflammation, promotes epithelial barrier repair, and shows excellent biocompatibility, outperforming both free BA and BZH nanoparticles. These findings position BZH@HCE as a versatile and effective platform for UC therapy, highlighting its potential as a natural, bioactive compound-based treatment.

The tumor microenvironment (TME), particularly its cancer-associated fibroblast (CAF)-driven fibrotic stroma and immunosuppressive components, forms intertwined physical and immune barriers that impede the efficacy of immunotherapy. To address this challenge, we developed a pH-gated hydrogel platform to modulate CAF-resulted TME barriers and activate potent antitumor immunity. This dynamic network, constructed by Schiff base crosslinking between carboxymethyl chitosan and aldehyde-functionalized hyaluronic acid, was utilized for the co-delivery of pirfenidone (PFD) and manganese-curcumin nanoparticles (MC). In the acidic TME, PFD was released rapidly from hydrogel to modulate CAF phenotype, thereby attenuating the formation of fibrotic stroma. The internalized MC orchestrated three synergistic therapeutic functions: (1) suppressing VEGF-mediated angiogenesis via curcumin, (2) generating reactive oxygen species through Mn²⁺-catalyzed Fenton-like reactions, and (3) promoting dendritic cell maturation by activating the cGAS-STING pathway with Mn²⁺. Upon 808 nm NIR laser irradiation, MC exhibited potent photothermal conversion efficacy, inducing localized hyperthermia that further amplified ROS production, and triggered immunogenic cell death. This coordinated cascade thereby elicited robust antitumor immunity, as evidenced by the upregulated expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-6) and enhanced CD8⁺ T cell infiltration. Notably, this strategy achieved marked tumor regression in B16F10 melanoma-bearing mice. Thus, this work established a TME-responsive platform that coordinated barrier modulation with multimodal therapeutic synergy, providing a promising paradigm for solid tumor immunotherapy. STATEMENT OF SIGNIFICANCE: Modulating the tumor microenvironment (TME) by targeting cancer-associated fibroblasts (CAFs) represent a promising strategy to enhance the efficacy of immunotherapy. Here, we develop a pH-gated hydrogel platform that enables the controlled delivery of pirfenidone and manganese-curcumin nanoparticles (MC), thereby facilitating the regulation of CAF-mediated fibrotic barriers followed by the activation of antitumor immunity. The released MC integrate antiangiogenic activity, ROS amplification, STING pathway activation, and photothermal ablation into a unified therapeutic system. Moreover, the photothermal effect further amplifies ROS generation and STING signaling, resulting in remodeling of the TME. This coordinated cascade elicits robust T-cell activation and cytokine secretion, achieving marked tumor eradication in murine melanoma models. Overall, this study establishes a therapeutic paradigm that integrates stromal barrier modulation with immune activation to achieve more effective tumor treatment.

The challenges of thermoplastic polyurethane (TPU) based ureteral stents are surface lubrication, bacterial adhesion, and Ca2+/Mg2+ ions deposition. In this work, a new amphiphilic copolymer for ureteral stent was reported to avoid the limitations of TPU ureteral stents. Poly(ε-caprolactone) (PCL) and polyethylene glycol (PEG) blocks were reacted with hexamethylene diisocyanate (HDI) to form amphiphilic multiblock copolymers (PCEU). The PCEU was extruded into ureteral stents (PCEU-Stent). The PEG blocks and PCL crystals aligned along the radial direction and resulted in phase-separated microstructures. The subsequent uniaxial stretching of the ureteral stents extended PCL crystals as physical crosslinkers to strengthen axial elasticity. Implantation of the stents in simulated body fluid induced surface migration of PEG, forming a PEG shielding layer around the ureteral stents. This surface reconstruction endowed the ureteral stents with excellent self-lubrication, resistance to bacterial adhesion, and effective inhibition of Ca2+/Mg2+ ions deposition.

Polyester-based biodegradable polymers are widely used in absorbable medical devices; however, the hydrophobic nature of polyesters limits their application in implantation under conditions requiring rapid degradation. This work reports poly(p-dioxanone) (PPDO) based short-term degradable polyurethanes with controllable degradation and mechanical properties. Three polyurethanes composed of poly(epsilon-caprolactone) (PCL), a poly(p-dioxanone)-poly(ethylene glycol)-poly(p-dioxanone) (PPDO-PEG-PPDO) triblock copolymer and polyethylene glycol (PEG) were synthesized with hexamethylene diisocyanate (HDI) as the chain-extender. The resulting polyurethanes exhibited a desirable balance of tensile strength (>20 MPa) and exceptional extensibility (elongation at break >1100%) as well as tunable stiffness (Young's modulus, 12-54 MPa). In artificial urine, the copolymers (PDEUs) exhibited composition-dependent mechanical degradation. The mechanical performance decreased in a near-linear time-dependent manner and the mechanical persistence times were 12, 34, and 52 days for PDEU1.5, PDEU3.5, and PDEU5.5, respectively. The structural analyses showed that the degradation was dominated by PPDO chain scission and depletion of a PPDO-rich amorphous phase, whereas PCL crystallinity provided structural stabilization. Additionally, PEG was largely retained to maintain the hydrophilicity of the degradation products. Overall, the degradation kinetics and mechanical lifetime of PDEUs could be tailored by adjusting PPDO/PCL compositions for providing hydrophilic copolymers with rapid and controllable degradation in biomedical applications.

Achieving concurrent aesthetic volume contouring and physiological healing remains a major hurdle in soft tissue reconstruction. While conventional hydrogels hold potential for soft tissue reconstruction, their clinical application is limited by insufficient mechanical durability for aesthetic volume contouring and a lack of bioactive signals for physiological healing. We engineered a structurally reinforced hydrogel (SFCC) where zinc crosslinked carboxymethyl chitosan microspheres bind to a thermal induced silk fibroin network, driving the formation of a coarsened fibrillar architecture. The microsphere reinforced fibrillar architecture facilitates the sustained release of zinc ions and endows the SFCC hydrogel with a significantly elevated storage modulus, superior antioxidant capacity, and robust angiogenic properties. In a rabbit intradermal implantation model, SFCC successfully activated dermal hair follicle regeneration, upregulated the expression of CD31 and Ki67, promoted collagen fiber deposition and enhanced cellular proliferation. Notably, SFCC decreased the Col I/Col III ratio by approximately 1.56-fold compared to the silk fibroin hydrogel. In a rat chronic burn model, SFCC accelerated healing by promoting macrophage polarization from the M1 to the M2 and stimulating fibronectin expression to orchestrate dermal epidermal junction reconstruction. The engineered SFCC hydrogel shows immense promise in integrated skin reconstruction, offering considerable potential to advance soft tissue repair therapies.

Impaired lipid metabolism and persistent accumulation of inflammatory macrophages represent major obstacles to effective anti-atherosclerotic (AS) therapy. To overcome the inherent limitations of conventional oral agents and nanocarrier-based systems, we developed a macrophage-targeted modulator by integrating curcumin (Cur) with gold nanoparticles (AuNPs). This construct was designed to concurrently correct dysregulated lipid homeostasis and suppress the expansion of pro-inflammatory macrophage populations. Specifically, protoporphyrin (Por) as a π-conjugated moiety was conjugated to polycaprolactone (PCL) via reactive oxygen species (ROS)-cleavable thioketal (TK) linkers, while AuNPs were functionalized onto hyaluronic acid (HA) backbones (HAPPT) to enable CD44-mediated foam cell recognition. Through self-assembly, Cur was efficiently loaded into the nano-system to yield the final modulator, Cur@HAPPT. Upon cellular uptake, Cur@HAPPT not only drove M1-to-M2 phenotypic repolarization but also provoked robust autophagic activation, collectively contributing to inflammation resolution. The autophagy-triggered cascade further facilitated lipid efflux and constrained inflammatory macrophage expansion, thereby producing a synergistic therapeutic benefit. Overall, Cur@HAPPT effectively attenuated AS progression and reinforced plaque stability, positioning this polymeric modulator as a promising targeted intervention for AS management.

This study developed an iron-substituted bioglass (BG) nanozyme that directly and efficiently catalyses the degradation of ethanol and acetaldehyde, achieving alcohol detoxification and the alleviation of intestinal injury. Specifically, the etching and substitution method increased the catalytic active sites while reducing ethanol metabolism byproducts.

Deep peripheral nerve regeneration is hindered by inflammatory infection, neurotrophic factor deficiency, and slow axonal growth kinetics. Although multifunctional nerve guidance conduits (NGCs) have been developed, achieving spatiotemporally precise neuromodulation within deeply located neural tissues remains a significant challenge. Herein, we developed a nerve conduit fabricated with a gut metabolite indole-3-propionic acid (IPA)-functionalized and polydopamine-coated Au nanorod clusters (AuNR@PDA-IPA (API)) loaded on a parallel fiber film of PLGA, exhibiting NIR-II-responsiveness for spatiotemporally precise neuromodulation. API nanoclusters convert deep-penetrating NIR-II light (1064 nm wavelength) into deeply localized heat (∼42-43 °C), which noninvasively activates the transient receptor potential vanilloid 1 (TRPV1) channel in Schwann cells (SCs). This activation triggers Ca2+ influx and membrane depolarization, promoting neurotrophic expression. Concurrently, NIR-II irradiation directly modulated the release of neuroprotective IPA from the API platform through an on-off switching mechanism. Meanwhile, IPA combined with PDA potently scavenged reactive oxygen species (ROS), suppressed NF-κB activation, and promoted M2 polarization of macrophages, thereby reshaping the neuroregenerative microenvironment. The in vitro and in vivo results demonstrate that API-functionalized conduit enhances VEGF-driven angiogenesis and activates SCs to upregulate the expression of neurotrophic factors (BDNF, NGF) and glial-specific proteins (S100, GFAPs). By orchestrated tripartite regulation of the "anti-inflammatory-angiogenic-neuroregenerative" system, the conduit enabled robust axonal regrowth, remyelination, and functional recovery in peripheral nerve defects, offering a transformative strategy for the repair of deeply located neural tissues. This work presents a noninvasive bioelectronic paradigm that merges spatiotemporal photothermal neuromodulation with immune metabolic reprogramming for precision neural reconstruction.

Esophageal diseases, including esophageal cancer and gastroesophageal reflux disease, remain major clinical challenges because of limited therapeutic efficacy and frequent treatment-related complications. Systemic treatments often suffer from insufficient drug accumulation at the lesion site and undesirable off-target effects, whereas endoscopic submucosal dissection (ESD), despite its effectiveness for early-stage lesions, is frequently complicated by postoperative esophageal stricture. These limitations underscore the need for localized and multifunctional therapeutic strategies. Owing to their excellent injectability, tunable physicochemical properties, and favorable biocompatibility, polysaccharide-based hydrogels, including those derived from chitosan, alginate, hyaluronic acid, and cellulose, have emerged as promising biomaterials for esophageal applications. As drug delivery systems, they enable localized and sustained therapeutic delivery with stimuli-responsive release capabilities, thereby enhancing therapeutic efficacy while minimizing systemic toxicity. In ESD, these hydrogels serve not only as submucosal injection agents to provide stable and sustained mucosal elevation but also as wound dressings that facilitate tissue regeneration, inhibit excessive fibrosis, and reduce the risk of postoperative stricture. The current challenges and future directions for the clinical translation of polysaccharide hydrogel-based platforms are also discussed. Collectively, it provides a comprehensive framework for the rational design and clinical development of polysaccharide hydrogel-based platforms to address the unmet therapeutic needs of esophageal diseases.

Chronic wounds are complicated by multidrug-resistant infections, oxidative stress, and prolonged inflammation, where single-mode antibacterial therapies are often inadequate. Here, we present a self-adaptive forming composite hydrogel (HP-BA@AD) that integrates direct bactericidal activity with host immune modulation for phase-specific wound healing. The polymer hydrogel HP-BA is constructed via dynamic boronate ester crosslinking between butyrate-modified polyvinyl alcohol and phenylboronic acid-functionalized oxidized hyaluronic acid, ensuring rapid gelation and strong adhesion to irregular wound beds. To enable controlled copper release and minimize cytotoxicity, reactive oxygen species (ROS)-responsive alginate-dopamine/Cu microspheres (AD) are incorporated. Under oxidative stress, AD releases Cu2+/Cu+ to amplify ROS, thereby enhancing macrophage phagocytosis and exerting bactericidal effects. Concurrently, butyrate is gradually liberated in acidic and enzymatic environments, suppressing mTOR signaling and reshaping cytokine profiles to promote immunemediated bacterial clearance. The butyrate-rich hydrogel exhibits strong bio-adhesion through hydrophobic interactions, while hydrolysis leads to reduced adhesion and facile removal. In vitro and in vivo experiments demonstrates that HP-BA@AD efficiently eradicates S. aureus, alleviates inflammation, enhances wound closure, and improves angiogenesis and collagen remodeling, ultimately restoring functional skin tissue. By combining material-host antibacterial synergy, tunable bio-adhesion, and self-adaptive therapeutic responses, HP-BA@AD offers a versatile strategy for treating infected chronic wounds.

The management of full-thickness infected wounds remains a major clinical challenge, largely due to the paucity of multifunctional dressings capable of stage-adaptive regulation across the entire healing cascade. To address this need, we developed a functionally graded bilayer polyurethane composite sponge. The upper layer was fabricated by chemical foaming combined with dopamine-assisted reduction, producing a hydrophobic macroporous sponge bearing a polydopamine coating and loaded with silver nanoparticles (PUF@P-Ag). The lower layer was a hydrophilic microporous polyurethane sponge (PUS) prepared by freeze-drying, which provided rapid hemostasis and controllable degradability. During the hemostatic phase, the PUS layer concentrated blood components to promote efficient clot formation and subsequently underwent rapid degradation. In the inflammatory phase, the acidic microenvironment generated by PUS degradation acted synergistically with sustained silver ion release from the upper layer and near-infrared photothermal effects, thereby establishing a triple antibacterial system. Concurrently, the polydopamine coating alleviated local oxidative stress. As healing progresses into the proliferation phase, a sustained weakly acidic milieu supported endothelial cell proliferation and angiogenesis. In a rat model of full-thickness infected skin defects, the bilayer sponge demonstrated sequential functional switching and synergistic activity, significantly accelerating wound closure, and promoting tissue remodeling and neovascularization.

The continuous spread of mpox disease caused by mpox virus (MPXV) has posed great threat to global public health. The postattachment membrane fusion process of MPXV is mediated by a multimeric protein machinery, termed as entry-fusion complex (EFC). Among EFC components, A30 and H2 are the earliest identified interaction pair and play important roles in virus entry. Here, we determine the crystal structure of MPXV A30/H2 subcomplex via the tandem-fusion strategy, and show that A30 undergoes large conformational rearrangements upon H2 binding. Structural analysis reveals extended intersubunit interface and highly conserved intermolecular interactions. In vitro binding data further clarify key residues and elements involved in the A30/ H2 subcomplex formation. Finally, we show that the H2-A30 fusion protein, superior to A30 ectodomain alone or the ectodomain-mixture of H2+A30, can induce more potent neutralizing-antibody responses which could inhibit viral infection. These data provide valuable information for the understanding of poxvirus EFC assembly and the H2-A30-based immunogen design and optimization.

The development of wound dressings with rapid hemostasis and sustained antibacterial activity is a critical challenge in wound management. In this work, a new strategy for fabricating antibacterial and hemostatic sponges as dressings is reported. Antibacterial agent polyhexamethylene biguanide (PHMB) was covalently bonded in the sponges via foaming. The introduction of PHMB improved the hydrophilicity and enhanced the hemostasis of sponges. The in vitro and in vivo evaluations in rat models of renal hemorrhage and tail amputation confirmed the exceptional hemostatic performance of sponges due to the cationic guanidine groups of PHMB, which promoted the adhesion and activation of red blood cells and platelets. The sponges demonstrated broad-spectrum antibacterial activity against both Staphylococcus aureus and Escherichia coli. In the full-thickness Staphylococcus aureus-infected wound models, the sponges exhibited the effective inhibition of bacterial infection and accelerated wound healing via facilitating re-epithelialization and collagen deposition.

Rational synthesis of nano-metal-organic frameworks (nano-MOFs) and their derivatives is crucial for tailoring structural and functional properties toward meet the demands of advanced energy applications. This review systematically categorizes synthesis strategies into precursor structure engineering and conversion engineering. The former, including solvothermal, modulation, templating methods and etc., enables precise control over morphology, porosity, and surface functionality of primary MOFs. The latter employs transformation pathways like pyrolysis and chemical conversion to produce derivatives with enhanced conductivity, robustness, and hierarchical porosity. By elucidating the underlying mechanisms, this study clarifies the relationship between synthetic control over size, configuration, and composition and key performance metrics (transport efficiency and stability) across key applications including electrocatalysis, batteries, and gas separation. Finally, current challenges and prospective research directions are discussed to guide the development of next-generation nano-MOF-based materials.

Hydrogen peroxide (H2O2) is a critical reactive oxygen species produced by cancer cells in response to drug stimulation, influencing cell behavior and providing feedback on treatment. However, current detection methods face challenges in achieving non-invasive, real-time and ultra-sensitive detection of low H2O2levels. This study introduces a novel photoanode-type sensor for H2O2detection, integrating cobalt metal-organic framework (Co-MOF) with n-type silicon nanowire arrays (n-SiNWs) via a one-step solvothermal method. The n-SiNWs serve as the photoanode, enhancing the specific surface area, while the Co-MOF shell broadens the optical absorption range and generates an internal electric field that improves carrier separation. This S-type heterojunction significantly boosts the photoelectric performance, achieving a detection range of 0.08-2000 mu M and a low limit of detection (LOD) of 0.023 mu M. The sensor utilizes photogenerated electrons for H2O2 reduction, enhancing sensitivity and stability in complex biological environments. Additionally, in mouse rectal cancer cells (CT26), the fluorescence of H2O2increased with doxorubicin concentration, correlating with the photocurrent response and confirming the sensor's effectiveness. This research establishes a highly sensitive and stable photo-electrochemical (PEC) sensor for monitoring H2O2in drug-stimulated cancer cells, advancing the development of effective cancer therapies.

Inflammatory bowel disease (IBD), a chronic gastrointestinal disorder with rising colorectal cancer risks, faces treatment challenges due to nonspecific drug delivery and systemic side effects. Recent advances focus on stimuli-responsive nanomaterials that enable targeted drug release at inflamed sites while sparing healthy tissues. This review examines progress in IBD nanotherapy over five years, first outlining IBD's pathophysiology and intestinal microenvironment. It systematically details nanomaterial designs responsive to internal triggers (pH, ROS/redox, enzymes) and external stimuli (temperature, light), as well as dual/multi-responsive systems that enhance tissue-nanocarrier interactions for precise drug targeting. These smart systems improve therapeutic efficacy by leveraging IBD-specific inflammatory signals to control drug release. The discussion extends to emerging strategies combining multiple stimuli to address IBD's complex microenvironment. While promising, challenges remain in optimizing biocompatibility, scale-up production, and clinical translation. Future opportunities lie in personalized nanotherapy and integration with diagnostics, potentially revolutionizing IBD management through enhanced specificity and reduced side effects.

Current biodegradable polymers for absorbable tissue ligation clips suffer from not possessing rigidity and toughness simultaneously compared with polyoxymethylene (POM) clips. To overcome the limitations, two series of biodegradable copolymers of poly(ε-caprolactone) and poly(L-lactide) with random and block architectures were designed and synthesized. Compared with random copolymer P(CL-r-LLA), diblock copolymer PCL-b-PLLA exhibited higher crystallinity and superior mechanical strength. The copolymers with 15 mol% CL composition were selected for further study, denoted as RP15 (random) and BP15 (block). The BP15 clips achieved a closure force of 27.9 ± 1.4 N, comparable to commercial POM clips (29.0 ± 2.4 N), while also offering biodegradability. The degradation studies showed that BP15 clips degraded slowly, maintaining structural integrity and sustained closure functionality for up to two weeks, which was essential for safe tissue ligation. Subcutaneous implantation in rats further confirmed that BP15 clips exhibited favorable performances, demonstrating their potential as a promising biodegradable alternative to POM for use as an absorbable tissue ligation clip.

This reviews MOF applications in electrochemical sensing, summarizes synthesis and performance of metal-based MOFs, and discusses sensor optimization strategies.