Biomaterials[JOURNAL]
Sun
200 papers
Identification and characterization of a Fibrillin-1 derived matrikine for cardiac regeneration and repair.
Edmunds KJ, Porter EC, Lai YR … +6 more , Guyette J, Williams C, Jaiganesh A, Ott H, Weinbaum JS, Black LD
Biomaterials · 2026 May · PMID 42214208 · Publisher ↗
The development of regenerative strategies to repair the heart is of high importance. Our lab has shown that extracellular matrix derived from decellularized fetal myocardium promotes neonatal cardiomyocyte proliferation...
The development of regenerative strategies to repair the heart is of high importance. Our lab has shown that extracellular matrix derived from decellularized fetal myocardium promotes neonatal cardiomyocyte proliferation in vitro. The goal of this study was to identify specific peptide(s)/protein(s) in solubilized cardiac ECM responsible for this proliferative effect. We hypothesized that isolation and then treatment with one or more small synthetic peptide derived from this source could replicate the cellular response to whole solubilized ECM. Decellularized fetal and adult rat hearts were fractionated by molecular weight using SDS-PAGE and transferred to PVDF membranes. Analysis of cardiomyocytes cultured on the membranes revealed regions of enhanced cardiomyocyte proliferation. Subsequent isolation and proteomic analysis of the protein bands that that correlated with proliferative regions identified fibrillin-1 as the predominant ECM protein associated with these regions of cardiomyocyte proliferation. One region (residues 55-86) of fibrillin-1 was synthesized as a peptide and tested for a direct effect on cardiomyocyte proliferation. Compared to positive and negative controls, as well as scrambled and alkylated versions, this peptide led to 3-4-fold increase in cardiomyocyte proliferation. Analysis of the amino acid sequence demonstrated high homology with latent-TGF-β binding proteins and subsequent experiments showed that the matrikine could also reduce TGF-β induced activation of cardiac fibroblasts. These data suggest that individual peptides derived from soluble ECM could have utility as a novel therapeutic for cardiac tissue engineering and regeneration.
Biomechanical and directional electric field coupling material promotes wound healing through Piezo1-mediated cell migration.
Fan Y, Lin M, Li J … +2 more , Yu Y, Huang Y
Biomaterials · 2026 May · PMID 42202626 · Publisher ↗
Re-epithelialization and extracellular matrix (ECM) regeneration determine the quality of wound repair. Although the physical microenvironment regulates these processes through physio-biochemical coupling, effective appr...
Re-epithelialization and extracellular matrix (ECM) regeneration determine the quality of wound repair. Although the physical microenvironment regulates these processes through physio-biochemical coupling, effective approaches are lacking. This study aims to reconstruct biomechanical and electric field microenvironments in wounds and is the first to develop a biomimetic coupling material that modulates wound mechanics and directional electric fields. The coupling material markedly accelerated re-epithelialization and promoted the ordered regeneration and structural remodeling of the ECM. Both axolotl skin-inspired biomechanical materials and application of electric fields at physiological intensities downregulated the expression of the mechanosensitive ion channel Piezo1 in keratinocytes, relieving its inhibitory effect on cell migration. This represents a new mechanism by which a biomimetic material with biomechanical and directional electric field coupling synergistically promotes keratinocyte migration. This study provides a novel strategy with translational potential for wound healing while offering theoretical insights and a versatile platform for research on wound regeneration.
Additive manufacturing and in vitro characterization of scaffolds consisting of PCL/PO-free bioactive glasses composites with angiogenic and osteogenic potential.
Nikody M, Dalfino S, Habibovic P … +6 more , Morejón L, Delgado JA, Tartaglia GM, Dolci C, Balmayor ER, Moroni L
Biomaterials · 2026 May · PMID 42202625 · Publisher ↗
The development of scaffolds with osteogenic and angiogenic properties represents an attractive strategy for regenerating large bone defects. This study describes the fabrication and characterization of bioactive glass-b...
The development of scaffolds with osteogenic and angiogenic properties represents an attractive strategy for regenerating large bone defects. This study describes the fabrication and characterization of bioactive glass-based composite scaffolds for bone regeneration applications. Scaffolds comprising polycaprolactone (PCL) and two different bioactive glasses (BGs), derived from white sand (BG-WS) and yellow sand (BG-YS), at an 80:20 wt% ratio were fabricated with a star-shaped pore geometry. Chemical characterization confirmed the presence of characteristic groups from PCL and BGs. The incorporation of BGs led to increased compressive moduli in the composites compared to PCL scaffolds only. Dissolution products, particularly from PCL/BG-YS, promoted enhanced vascular pattern formation of human umbilical endothelial vein cells (HUVECs) co-cultured indirectly with human mesenchymal stromal cells (hMSCs). Direct culture of hMSCs on PCL/BG-WS and PCL/BG-YS composite scaffolds resulted in greater VEGFA production compared to PCL scaffolds alone. The expression of the early osteogenic marker RUNX2 was upregulated on day 7 in response to both composite scaffolds, while ALPL expression increased only with the PCL/BG-WS scaffolds on day 28. Additionally, late osteogenic gene markers (COL1A1 and OCN) were both upregulated on day 28 in PCL/BG-WS scaffolds. Lastly, the measurement of analytes secreted by hMSCs showed higher secretion levels on day 7 than 28, with PCL scaffolds yielding higher concentrations of IL-10, TNF-α, and CCL2 than composite scaffolds. Overall, both PCL/BG-WS and PCL/BG-YS scaffolds demonstrated osteogenic, angiogenic, and potential immunomodulatory properties. Notably, PCL/BG-WS exhibited the strongest osteogenic responses, which may be attributed to its Ti ion content, highlighting the critical role of BG composition in modulating the biological performance of the composites. The findings of this study indicate that combining naturally-derived PO-free BGs with PCL to fabricate 3D composite scaffolds enhances osteogenic and angiogenic properties of the final constructs, emphasizing their potential in bone regeneration.
A dual zinc-complexation nanozyme performs synergistic chemodynamic-immunotherapy along with additional immunosuppressive microenvironment remodeling and immune evasion inhibition for efficient breast cancer treatment.
Zhang H, Wang H, Wang H … +5 more , Liu T, Mu W, Shi X, Weng L, Chen X
Biomaterials · 2026 May · PMID 42190516 · Publisher ↗
The clinical application of nanozyme mediated chemodynamic-immunotherapy is regretfully hindered because of inadequate immunogenic cell death, immunosuppressive microenvironment and robust immune evasion of tumor cells,...
The clinical application of nanozyme mediated chemodynamic-immunotherapy is regretfully hindered because of inadequate immunogenic cell death, immunosuppressive microenvironment and robust immune evasion of tumor cells, which normally lead to the tumor metastasis and recurrence even after therapy. Herein, an engineered nanozyme (ZSTH) with core-shell-corona structure was fabricated to overcome above drawbacks for effective treatment of both primary and metastatic breast cancer via zinc-nanozyme mediated nanocatalytic medicine, Zn enhanced immunotherapy along with a reversion of immunosuppressive microenvironments, and brefeldin A (BFA, disruptor of Golgi apparatus)-induced immune escape inhibition. The ZSTH consisted of BFA-loaded nanozyme with dual zinc-complexation modes (ZS) as core, triphenylphosphine (TPP, target agent for mitochondria) grafted phospholipid as shell and hyaluronic acid (HA, target agent for tumor cells) as corona. During therapy, the nanozyme first accumulated in tumor cells via enhanced permeability and retention effect and HA-mediated tumor targeting. After intratumoral biodegradation of HA corona, the ZSTH rapidly disintegrate into ZST nanozyme, Zn and BFA. The ZST enter mitochondria and perform chemodynamic therapy to induce immunogenic cell death (ICD) for inhibiting tumor growth and metastasis. Simultaneously, the Zn activated Caspase-1/GSDMD-dependent pyroptosis pathway, resulting in the enhancement of ICD processes. In addition, the Zn-overloading also reduced NAD expression to inhibit glycolysis process, causing the macrophages polarization from M2-to-M1 type to reverse tumor immunosuppressive microenvironment. Moreover, BFA further disrupted the Golgi apparatus (GA) to inhibit the PD-L1 production and PD-L1 mediated immune escape, which could be enhanced by the Ca capture property of ZST via disruption of Ca homeostasis in GA. Both in vitro and in vivo results indicated the high efficacy of ZSTH nanozyme in suppressing tumor growth and metastasis, offering a promising strategy for breast cancer treatment.
Nanoparticles-mediated dual metabolic-immunological intervention reverses immunosuppression in muscle invasive bladder cancer.
Chen J, Ding Z, Lai S … +4 more , Gan Z, Wang W, Jiao B, Yu Q
Biomaterials · 2026 May · PMID 42190515 · Publisher ↗
Muscle-invasive bladder cancer (MIBC) is an aggressive urological malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) driven by dysregulated oncogenic metabolism. The oxidoreductase NA...
Muscle-invasive bladder cancer (MIBC) is an aggressive urological malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) driven by dysregulated oncogenic metabolism. The oxidoreductase NAD(P)H:quinone oxidoreductase 1 (NQO1) stabilizes the core metabolic regulator hypoxia-inducible factor 1α (HIF-1α), which further transcriptionally activates the homeobox transcription factor SIX1, forming a coordinated NQO1/HIF-1α/SIX1 signaling axis that drives metabolic reprogramming and immune evasion in MIBC, yet targeted therapies disrupting this metabolic-immune nexus remain clinically unavailable. Here, we developed a biomimetic macrophage membrane-cloaked nanoplatform (MMP@siN/NC) for targeted co-delivery of NQO1-targeting siRNA (siNQO1) and the SIX1 small-molecule inhibitor NCGC, with a PEG-PDLLA/DOTAP hybrid core enabling prolonged systemic circulation, enhanced tumor targeting, efficient cellular internalization, facilitated endosomal escape, and synergistic drug release. In vitro, MMP@siN/NC exerted robust cytotoxicity against MIBC cells, induced potent immunogenic cell death (ICD), and suppressed aerobic glycolysis and tricarboxylic acid (TCA) cycle flux via axis blockade, which further promoted dendritic cell maturation, M1 macrophage polarization, and tumor-specific T-cell priming. In vivo, MMP@siN/NC potently inhibited tumor growth, elicited a systemic abscopal effect, and established durable anti-tumor immune memory in subcutaneous MIBC models, with strong synergistic efficacy in combination with anti-CTLA-4 (αCTLA4) immune checkpoint blockade. Critically, in a clinically relevant orthotopic MIBC model, the nanosystem exhibited excellent tumor accumulation, significant therapeutic efficacy, prolonged survival, and a favorable safety profile. Collectively, this work validated the NQO1/HIF-1α/SIX1 axis as a targetable metabolic-immune driver in MIBC, and presented a translatable nanotherapeutic strategy to simultaneously disrupt tumor metabolism and reactivate anti-tumor immunity for MIBC treatment.
AIE-Pt metallacages with water-sensitized type I photodynamics for enhanced cancer therapy.
Li W, Zhu ZH, Hu Y … +2 more , Tang BZ, Feng G
Biomaterials · 2026 Nov · PMID 42184752 · Publisher ↗
Photodynamic therapy (PDT) offers precise cancer treatment, yet conventional photosensitizers frequently suffer from aggregation-caused quenching (ACQ) and oxygen dependence. Here, we report a platinum (Pt)-modulated sup...
Photodynamic therapy (PDT) offers precise cancer treatment, yet conventional photosensitizers frequently suffer from aggregation-caused quenching (ACQ) and oxygen dependence. Here, we report a platinum (Pt)-modulated supramolecular metallacage, TPE-Pt-Cage, constructed from aggregation-induced emission (AIE) ligands to overcome these limitations. Pt coordination rigidifies the AIE framework at the molecular level, suppressing intramolecular motions and π-π stacking, while the resulting supramolecular assembly adopts an open architecture with accessible cavities that facilitates oxygen and substrate diffusion. These synergistic structural features empower TPE-Pt-Cage to achieve ROS generation efficiencies far exceeding its precursor and leading commercial photosensitizers under light irradiation. Under hypoxia, TPE-Pt-Cage engages a sequential electron-transfer pathway in which water acts as the oxygen source, producing in situ O that is subsequently converted into O• and •OH. This mechanism is supported by hypoxia-tolerant radical species production and redox potentials sufficient to oxidize HO, enabling dominant type I ROS output when external oxygen is scarce. Together with the intrinsic chemotherapeutic activity of Pt, TPE-Pt-Cage achieves synergistic tumor inhibition in vitro and in vivo. This hypoxia-resilient PDT strategy, combined with Pt-mediated chemotherapy, drives potent tumor suppression and defines a generalizable design principle for developing AIE-based metallacages as effective PDT agents in oxygen-deficient solid tumors.
Multifunctional antibacterial intelligent hydrogel for infection detection and inflammation regulation to promote diabetic wound healing.
Yang B, Cheng Q, Zhao S … +8 more , Tang Y, Pang E, Chen Y, Zhu P, Wang C, Jin S, Lan M, Tan C
Biomaterials · 2026 Nov · PMID 42184751 · Publisher ↗
Infection remains a major barrier to diabetic wound repair and can lead to severe complications. Therefore, timely infection detection, effective antibacterial therapy, and sustained inflammation regulation are critical...
Infection remains a major barrier to diabetic wound repair and can lead to severe complications. Therefore, timely infection detection, effective antibacterial therapy, and sustained inflammation regulation are critical for successful wound healing. Here, we developed an intelligent hydrogel dressing that enables fluorescence-based infection indication while simultaneously providing coordinated antibacterial and anti-inflammatory therapy. The injectable hydrogel was constructed via dynamic boronate ester crosslinking between polyvinyl alcohol and phenylboronic acid-modified chitosan, and functionalized with BODIPY-loaded mesoporous polydopamine nanoparticles (mPDA@BP) and the fluorogenic substrate 4-Methylumbelliferyl-β-D-glucuronide (MUG). Upon cleavage of MUG by bacteria-secreted β-glucuronidase, the released 4-methylumbelliferone emits a blue fluorescence signal, enabling rapid visualization of infection progression. Meanwhile, mPDA@BP generates reactive oxygen species under light exposure for photodynamic antibacterial therapy, while maintaining sustained anti-inflammatory immunomodulation in the dark condition. Benefiting from its dynamic network, the hydrogel exhibits excellent injectability and conformal adaptability to irregular wound geometries. In an infected diabetic mouse wound model, this hydrogel significantly reduced bacterial burden and inflammatory responses, accelerated wound closure, and enhanced epidermal regeneration, collagen deposition, and angiogenesis. Collectively, this work presents a cost-effective theranostic hydrogel platform for integrated infection monitoring and coordinated diabetic wound therapy.
Polysaccharide-mediated in vivo cascade chemistry converts endogenous Cu(II) into copper nanoclusters as super nanozymes for Parkinson's disease treatment.
Chen S, Zhang X, Yu Z … +1 more , Chang B
Biomaterials · 2026 Nov · PMID 42184750 · Publisher ↗
The causes of Parkinson's disease (PD) so far are controversial, but its chronic nature and epidemiological studies reveal that dyshomeostasis of copper biometals is greatly responsible for the progressive dysfunctions t...
The causes of Parkinson's disease (PD) so far are controversial, but its chronic nature and epidemiological studies reveal that dyshomeostasis of copper biometals is greatly responsible for the progressive dysfunctions that could fuel a vicious cycle of multiple pathogenic factors throughout PD trajectory. Unfortunately, current medication will exert non-specific removal of copper ions including biologically essential static copper pool in metalloenzyme, further exacerbating the neurotoxic effect associated with copper dyshomeostasis. Here, we reported a cascade neuroprotective therapy, which only utilized polysaccharides (i.e. thymine grafted hyaluronic acid, denoted as TgHA) to transform endogenous neurotoxic Cu(II) ions into red-emissive few-atom copper clusters while leaving the levels of essential biometals unchanged. Moreover, these copper clusters can functionally mimic three main antioxidant enzymes to protect neuronal cells from oxidative damage. In PD mouse model, about 83% of travel distance and 61% of fall latency restored back to normal mice after intraperitoneal injection of TgHA alone, clearly alleviating motor dysfunctions. We envisioned polysaccharide-mediated in vivo cascade chemistry will shift therapeutic paradigm in biometal-involved neurological disorders.
A photo-responsive, fisetin-functionalized DNA nanocage for programmed therapy to accelerate early-stage wound healing in aged skin.
Yue Z, Jiang Z, Yang Y … +4 more , Yin W, Lin Y, Gao Y, Cai X
Biomaterials · 2026 Nov · PMID 42184749 · Publisher ↗
Age-related impaired wound healing presents distinct challenges compared to conventional wounds, primarily due to dysregulated phase kinetics of wound repair and chronic cellular senescence, which collectively disrupt th...
Age-related impaired wound healing presents distinct challenges compared to conventional wounds, primarily due to dysregulated phase kinetics of wound repair and chronic cellular senescence, which collectively disrupt the dynamic and orderly progression of tissue regeneration. Effective intervention requires a stage-specific and temporally programmed therapeutic strategy. To address this, we first performed transcriptome sequencing (RNA-seq) to elucidate the differential healing trajectory between young and aged wounds. Herein, we construct a photo-responsive, Fisetin-functionalized DNA nanocage (TAF) for spatiotemporally precise therapy of aged wounds. TAF is composed of a tetrahedral DNA nanocage loaded with a miR-29-targeting antisense oligonucleotide (ASO) covalently linked through a photocleavable linker and noncovalently encapsulating the senolytic agent Fisetin. The TAF platform enables a programmed therapeutic strategy: (a) the intrinsic antioxidant capacity of DNA scavenges excessive reactive oxygen species (ROS) during the early inflammatory phase; (b) photo-triggered ASO release in the proliferative phase promotes collagen synthesis; and (c) sustained Fisetin release eliminates senescent cells, fostering a pro-regenerative microenvironment. In vivo studies in aged mice reveal that TAF-mediated therapy significantly accelerates early wound closure and enhances high-quality tissue regeneration. In summary, TAF establishes an efficient nanomedicine platform that improves aged tissue repair through stage-specific, temporally programmed regulation.
A silk fibroin-based nanomodulator reshapes periodontal bone immunity by flipping the metabolic switch in macrophages to promote periodontal tissue regeneration.
Wang H, Ma Y, Song Y … +8 more , Huang Y, Ma X, Hu Y, Zhou P, Chen Y, Cai R, Xu X, Tao G
Biomaterials · 2026 Nov · PMID 42184748 · Publisher ↗
Periodontitis involves chronic inflammation with dysfunctional macrophage metabolism. To address this, we uniquely combined the biological properties of silk fibroin with a desolvation method and biomineralization princi...
Periodontitis involves chronic inflammation with dysfunctional macrophage metabolism. To address this, we uniquely combined the biological properties of silk fibroin with a desolvation method and biomineralization principles, developing a multifunctional nanocomposite termed SF-HA@TA-Mn. It was engineered to function as a nanomodulator of intracellular metabolism. This system utilizes TA for mitochondrial targeting and Mn ions for enhanced antioxidant activity, enabling precise scavenging of mtROS. By restoring mitochondrial homeostasis, the nanomodulator effectively reprograms macrophage metabolism, shifting polarization from a pro-inflammatory M1 to a reparative M2 phenotype, thereby remodeling the local immune microenvironment. Integrated multi-omics analyses revealed the nanomodulator primarily reprograms arginine metabolism by downregulating the JAK2-STAT1-ASS1 axis, while reversing inflammatory alterations in glutamine-fueled TCA cycle and purine metabolism. Additionally, it inhibits inflammatory damage in hPDLSCs and uses the osteoconductive property of SF-HA to synergistically couple immunomodulation with osteogenic differentiation. In vivo evaluation using a rat periodontitis model confirmed the dual efficacy of SF-HA@TA-Mn NPs, demonstrating significant anti-inflammatory effects and enhanced alveolar bone regeneration. By flipping the macrophage metabolic switch toward a reparative state, the nanomodulator effectively reverses the inflammatory oxidative stress cycle, actively promoting bone regeneration, and thereby offers a promising integrated therapeutic platform for periodontitis management.
Modularly designed hybrid vesicles as dual-adjuvant nanovaccines for cancer immunotherapy.
Pan Y, Tang Y, Chen L … +7 more , Xu Y, Hu X, Zhang J, Zheng Y, She P, Rao L, Xu X
Biomaterials · 2026 May · PMID 42184558 · Publisher ↗
Natural extracellular vesicles (EVs) and extruded membrane vesicles (MVs) have emerged as a promising platform for cancer vaccination by co-delivering tumor antigens and adjuvant. However, conventional designs rely on a...
Natural extracellular vesicles (EVs) and extruded membrane vesicles (MVs) have emerged as a promising platform for cancer vaccination by co-delivering tumor antigens and adjuvant. However, conventional designs rely on a single class of adjuvant, which often fail to adequately activate dendritic cells (DCs), resulting in inefficient cross-priming and weak cytotoxic T lymphocyte (CTL) activation. To address this, we designed a dual-adjuvant nanovaccine by modularly fusing interferon-alpha (IFNα)-displaying bacterial MVs (IFNα-BMVs) with programmed cell death protein 1 (PD1)-displaying cancer MVs (PD1-CMVs) to potentiate antitumor immune responses. In this design, IFNα-BMVs deliver dual-adjuvant pathogen-associated molecular patterns (PAMPs) and IFNα to promote DC maturation and cross-priming, thereby activating CTL. Concurrently, PD1-CMVs provide tumor-associated antigens (TAAs) and utilize membrane-anchored PD1 as a decoy receptor for targeted PD-L1 blockade, thus preventing CTL exhaustion. More importantly, this IFNα and PD1 co-displaying hybrid MVs (IP-HMVs) nanovaccine significantly upregulated costimulatory molecules and antigen-presenting molecules, thereby promoting DC maturation and CTL infiltration. Furthermore, RNA sequencing analysis validated that IP-HMVs robustly activated canonical antigen presentation pathways. In both subcutaneous and metastatic 4T1 tumor models, IP-HMVs significantly suppressed tumor progression and extended median survival to 35 days. The modular design offers a generalizable framework for developing next-generation cancer vaccines.
Electron-permeable graphitic atomic barrier confers paradoxical enhancement of fibrosarcoma apoptosis by Ptzymes.
Dong Q, Li Z, Xiao J … +4 more , Li C, Zeng J, Xu J, Chen Z
Biomaterials · 2026 May · PMID 42184557 · Publisher ↗
Fibrosarcoma, a highly invasive sarcoma with redundant apoptotic networks, exhibits profound resistance to conventional therapies. Platinum nanozymes (Ptzymes) combine DNA-damaging activity with catalytic redox modulatio...
Fibrosarcoma, a highly invasive sarcoma with redundant apoptotic networks, exhibits profound resistance to conventional therapies. Platinum nanozymes (Ptzymes) combine DNA-damaging activity with catalytic redox modulation; however, their application is limited by uncontrolled catalytic activity and off-target toxicity. This design effectively suppresses Pt ion leakage while preserving catalytic activity, enabling more controlled oxidative stress modulation. Pt@G NPs exhibit enhanced cytotoxicity toward HT1080 fibrosarcoma cells (120%) compared with bare Ptzymes, while showing reduced cytotoxic responses in three normal cell lines (80%). Cellular uptake studies revealed clear cell type-dependent differences, with HT1080 cells displaying the highest Ptzymes internalization. Furthermore, transcriptomic analysis indicated that ROS-related pathways were more prominently altered in Pt@G-treated HT1080 cells compared with the Pt-treated group, accompanied by increased ROS levels and lipid peroxidation. These changes were accompanied by activation of apoptosis-related processes. In vivo, Pt@G NPs achieved effective suppression of HT1080 xenograft tumors with improved systemic tolerance, as evidenced by reduced inflammatory cytokine levels and preserved hepatic and renal function. Overall, this study demonstrates that graphitic shell-confined Ptzymes can modulate intracellular oxidative stress responses and enhance therapeutic performance, providing a promising strategy for balancing therapeutic efficacy and biosafety.
Sprayable polysaccharide-based biomimetic double dressing with synergistic regulation for wound healing.
Xue Y, Lin Y, Lu Y … +13 more , Zhang H, Chen B, Zhao Y, Wu H, Xu S, Zhan K, Zhou J, Cai X, Zhou Q, Chen C, Jin L, Tang X, Zheng Y
Biomaterials · 2026 May · PMID 42184556 · Publisher ↗
Current sprayable hydrogel dressings often fail to achieve the functional integration required for complex wounds, owing to inherent design flaws and a lack of synergistic action, which delays healing and promotes scarri...
Current sprayable hydrogel dressings often fail to achieve the functional integration required for complex wounds, owing to inherent design flaws and a lack of synergistic action, which delays healing and promotes scarring. Inspired by the stratified structure and dynamic repair functions of human skin, we developed a sprayable, biomimetic double-layer polysaccharide dressing (BDD) that integrates the immunomodulatory compound mangiferin (MGF). This integrated system, termed MGF@BDD, rapidly self-assembles via sequential spraying, offering adhesion and wound adaptability. The distinctive strength of MGF@BDD is its spatiotemporally coordinated bioactivity, enabled by synergistic regulation between its layers in response to the dynamic wound microenvironment. The dense top layer, reinforced by Ca-Ba dual-ion coordination, provides immediate hemostasis and enzyme-resistant mechanical protection. In contrast, the porous bottom layer acts as an intelligent reservoir for MGF, maintaining a regenerative niche. During the inflammatory phase, the acidic environment triggers the hydrolysis of dynamic bonds within the bottom-layer, accelerating MGF release for anti-inflammatory and anti-oxidative effects, while Ca-Ba ions released from the top layer synergistically suppress inflammation at its source. As healing progresses into the proliferative phase, the network stabilizes under neutral conditions, switching to the sustained co-release of MGF and Ca to effectively promote angiogenesis and tissue remodeling. Both in vitro and in vivo experiments have confirmed that MGF @BDD can effectively promote wound healing, as evidenced by significantly accelerated wound closure and reduced collagen disorder. Constructed via a simple two-syringe process, this work presents an adaptive system capable of dynamically regulating the healing cascade, offering a novel strategy for the functional regeneration of complex wounds.
Janus TiO-CoO heterojunction enabling sonodynamic driving multi-pathway cell death for enhanced immune activation.
Cheng Z, Ning M, Zhu Y … +3 more , Tian R, Jia F, Chen H
Biomaterials · 2026 Nov · PMID 42176394 · Publisher ↗
Tumor heterogeneity induces resistance of programmed cell death (PCD), together with a highly immunosuppressive tumor microenvironment (TME), collectively constraining the efficacy of cancer therapies. Herein, a Janus Ti...
Tumor heterogeneity induces resistance of programmed cell death (PCD), together with a highly immunosuppressive tumor microenvironment (TME), collectively constraining the efficacy of cancer therapies. Herein, a Janus TiO-CoO@PEG nanoplatform featuring a Z-scheme heterojunction was developed as a novel sonosensitizer, enabling efficient ultrasound-induced charge separation to boost sonodynamic therapy (SDT) activity. Moreover, the obtained TiO-CoO@PEG was endowed with multienzyme activity, including glutathione (GSH) oxidase- and catalase-like activities, which could regulate TME (e.g., relieve hypoxia), amplify oxidative stress, and collaboratively break intracellular redox homeostasis, thereby dismantling tumor defense barriers. More interestingly, upon ultrasound (US) irradiation, SDT together with chemodynamic therapy (CDT) was found to concurrently activate three programmed cell death pathways, i.e., apoptosis, ferroptosis, and pyroptosis to overcome tumor treatment resistance. This multiple death-pathway efficiently induced immunogenic cell death (ICD), promoting the release of damage-associated molecular patterns (DAMPs) and inflammatory cytokines. As a result, the in vivo tumor growth was significantly suppressed and the immunosuppressive TME was remodeled, as characterized by tumor-associated macrophages (TAMs) polarizing towards the M1 phenotype, maturation of dendritic cells (DCs), infiltration of abundant cytotoxic T lymphocytes (CTLs), and depletion of regulatory T cells (Tregs), which ultimately impeded the formation of distant lung metastases. Collectively, this work presents a sonodynamic-immunotherapeutic synergistic strategy based on Janus heterojunction nanoparticles to induce multi-pathway cell death and immune activation, offering a promising solution to overcome treatment resistance and achieve sustained systemic antitumor immunity.
Regorafenib and R837 nanoparticle-stabilized Pickering emulsions overcome the angiogenesis-immune tolerance axis in transarterial chemoembolization.
Peng Y, Liu H, Yang L … +10 more , Wu X, Fan J, Liang X, Cao L, Miao M, Chen H, Teng M, Li Z, Liu G, Cheng H
Biomaterials · 2026 Nov · PMID 42176393 · Publisher ↗
Transarterial chemoembolization (TACE) is hindered by the instability of embolic agents, as well as the tumor microenvironment post-embolization, which is characterized by angiogenesis and immune tolerance. Here, we iden...
Transarterial chemoembolization (TACE) is hindered by the instability of embolic agents, as well as the tumor microenvironment post-embolization, which is characterized by angiogenesis and immune tolerance. Here, we identify a coupled angiogenesis-immune tolerance axis as a key mechanism underlying post-TACE therapeutic resistance. In this study, we developed a novel combination formulation of regorafenib and R837 designed to reprogram the tumor microenvironment following embolization. Using a supercritical carbon dioxide-assisted method, we successfully synthesized carrier-free pure drug nanoparticles of regorafenib and R837, achieving nanoparticles-stabilized lipiodol Pickering emulsions (PE-RR) preparation. This stable formulation not only significantly enhances the embolic stability and sustained drug release, but also effectively reverses post-embolization hypoxia, angiogenesis and immune tolerance through the therapeutic combination of regorafenib and R837. This study demonstrated that locoregional therapy with PE-RR significantly suppressed the hypoxia-angiogenesis signaling axis. These effects are mediated by the coordinated inhibition of angiogenesis (HIF-1α/VEGF axis) and activation of anti-tumor immunity, establishing a mechanistic linkage between vascular normalization and immune reprogramming. By strengthening antigen release and localized delivery of immune agonists, PE-RR facilitated anti-tumor immune activation and improved the therapeutic response to embolization, overcoming the adverse tumor microenvironment associated with conventional lipiodol embolization. Additionally, in bilateral tumor models, PE-RR could boost the therapeutic efficacy of PD-1 checkpoint blockade, increase the generation of anti-tumor immune memory and minimize the low responsiveness of immune checkpoint inhibitors in liver cancer. The stable Pickering embolic emulsion offers an innovative approach for the clinical translation of embolization therapy.
Sequential redox control and SDF-1α release by diselenide-bridged mesoporous silica nanoparticles promote intervertebral disc regeneration.
Wei Z, He M, Liang J … +9 more , Zhang W, Xie X, Le S, Dai M, Liu J, Zhou Y, Shao D, Yang C, Wang L
Biomaterials · 2026 Nov · PMID 42167007 · Publisher ↗
Intervertebral disc degeneration (IVDD) is characterized by overactive oxidative stress, uncontrolled inflammation, and the deterioration of extracellular matrix (ECM). Deciphering the spatiotemporal cues of the complica...
Intervertebral disc degeneration (IVDD) is characterized by overactive oxidative stress, uncontrolled inflammation, and the deterioration of extracellular matrix (ECM). Deciphering the spatiotemporal cues of the complicated microenvironment would facilitate the development of new therapeutic strategies. In this study, we reveal that increased expression of oxidative stress markers is strongly associated with pro-inflammatory markers at the early stage, whereas the level of ECM repair markers is elevated at the late stage. Hypothesizing that sequentially targeting redox, inflammation, and ECM repair would be beneficial to IVDD management, we report the development of diselenide-bridged mesoporous silica nanoparticles (MSNs) loaded with SDF-1α. Redox-responsive MSNs not only efficiently neutralize ROS in damaged nucleus pulposus (NP) cells and macrophages to ameliorate oxidative stress and inflammation at the early stage via inhibiting the NF-κB pathway, but also sequentially release SDF-1α to facilitate ECM repair at the late stage via activating the PI3K-AKT-mTOR pathway. Leveraging such a time-sequenced microenvironment regulation mechanism, MSN@SDF-1α attenuates inflammation, maintains NP water content, and induces mesenchymal stem cells (MSCs) homing, leading to the structural regeneration of intervertebral discs in a puncture model. Our study proposes a mechanism-driven therapeutic approach that integrates insights into redox, inflammation, and ECM repair with the advanced design of versatile bioactive materials, offering a promising strategy for precise intervertebral disc regeneration.
Gradient intrafibrillar mineralized collagen scaffold promotes osteochondral regeneration by enhancing differentiation of SCRG1 progenitor cells.
Huang B, Wu Z, Zhang T … +13 more , Cheng L, Ren Y, Hong F, Chen X, Zhang X, Zhang H, Bao F, Zhang H, Zhu S, Chen X, Liu H, Ouyang H, Zhou J
Biomaterials · 2026 Nov · PMID 42167006 · Publisher ↗
Osteochondral defects arising from trauma, joint diseases, or aging remain a major challenge in orthopedics. Native osteochondral tissue possesses a highly ordered biphasic gradient architecture; however, current biomime...
Osteochondral defects arising from trauma, joint diseases, or aging remain a major challenge in orthopedics. Native osteochondral tissue possesses a highly ordered biphasic gradient architecture; however, current biomimetic scaffolds often fail to simultaneously recapitulate its macro- and microstructural features. Inspired by the mineralized transition zone at the natural osteochondral interface, we developed an integrated biomimetic mineralized hydrogel scaffold with gradient mineral distribution and intrafibrillar mineralization via a bottom-up strategy combining ultrasmall calcium phosphate polymer-induced liquid precursor (CaP-PILP) and collagen molecular self-assembly. Transmission electron microscopy and energy-dispersive X-ray spectroscopy revealed a gradient mineralization profile of collagen fibers within an approximately 20 μm interface, with calcium content gradually increasing from 5.13% to 24.05%. The scaffold supported the viability of human bone marrow mesenchymal stromal cells (hBMSCs) and effectively promoted their osteochondral lineage differentiation in vitro. RNA sequencing identified the calcium-mediated ERK signaling pathway as a key regulator of this process. In a knee osteochondral defect model of adult New Zealand White rabbits, micro-CT and histological analyses demonstrated that the IMC group significantly enhanced subchondral bone formation (BV/TV: 23.40 ± 5.63% and Tb.Sp: 0.112 ± 0.056 mm at 12 weeks) and cartilage regeneration (with markedly increased expression of COLLAGEN II and AGGRECAN) compared with the pure collagen and extrafibrillar mineralization control. Mechanistically, the scaffold activated the calcium-mediated ERK/TGF-β signaling pathway in vivo, directing SCRG1+ progenitor cells toward osteochondral differentiation and thereby facilitating tissue repair. By integrating physical support with biological induction, this gradient mineralized scaffold offers a promising strategy for osteochondral defect regeneration.
Biomimetic nanozyme reverse the Warburg effect to empower intrahepatic cholangiocarcinoma immunotherapy.
Zhu Y, Duan Y, Dai L … +9 more , Liu B, Lv M, Lin J, Li Y, Qiu Y, Cheng R, Lu S, Duan Y, Sun Y
Biomaterials · 2026 Nov · PMID 42167005 · Publisher ↗
Intrahepatic cholangiocarcinoma (ICC) is notoriously resistant to treatment, largely due to a "cold" microenvironment shaped by the Warburg effect. This metabolic signature leads to excessive lactate buildup, which acts...
Intrahepatic cholangiocarcinoma (ICC) is notoriously resistant to treatment, largely due to a "cold" microenvironment shaped by the Warburg effect. This metabolic signature leads to excessive lactate buildup, which acts as a physical and chemical shield against T-cell infiltration. To breach this barrier, we developed ultrasound-activated GdMnO (GMO) perovskite nanozymes that forcibly reverse the Warburg effect by accelerating the lactate-to-pyruvate metabolic switch. Through Gd-incorporating, we optimized the Mn-based electronic structure to achieve high-efficiency lactate catabolism, which is pulsed by ultrasound to maximize enzymatic turnover. This intervention does not merely deplete lactate; it reshapes the tumor's "bioenergetic engine" from glycolytic acidification toward mitochondrial oxidation. When cloaked in M1 macrophage membranes (GMO@M), these nanozymes selectively accumulate in ICC tissues. The subsequent Mn release triggers the cGAS-STING pathway, synergizing with the metabolic shift to flip the immunological status of the tumor. Combined with αPD-L1, this ultrasound-driven metabolic recalibration yields potent systemic immunity and durable tumor regression. Our findings demonstrate that targeting the Warburg effect via responsive nanozymes is a decisive strategy for sensitizing recalcitrant ICC to immunotherapy.
Stimulus-responsive engineered oncolytic bacteria.
Chen J, Liu Y, Wu Y … +1 more , Liu Z
Biomaterials · 2026 Nov · PMID 42160954 · Publisher ↗
Oncolytic bacteria have emerged as a promising platform for targeted cancer therapy owing to their intrinsic ability to preferentially colonize tumor tissues, induce direct tumor cell killing, and remodel the tumor micro...
Oncolytic bacteria have emerged as a promising platform for targeted cancer therapy owing to their intrinsic ability to preferentially colonize tumor tissues, induce direct tumor cell killing, and remodel the tumor microenvironment to activate antitumor immunity. However, native bacteria alone rarely meet the requirements of precision oncology, particularly in terms of spatial specificity, temporal control, and safety. Recent advances in synthetic biology have enabled the construction of stimulus-responsive gene circuits that confer programmable control over therapeutic gene expression in tumor-colonizing bacteria by coupling defined exogenous triggers or endogenous tumor-associated cues to tightly regulated genetic programs. These engineered systems support the tumor-specific delivery of diverse therapeutic payloads, including cytotoxic agents, cytokines, immunomodulatory ligands, prodrug-converting enzymes, metabolic modulators, and nucleic acid-based therapeutics, while minimizing off-target activity. This review thus summarizes recent developments in stimulus-responsive oncolytic bacteria, highlights key design principles and performance trade-offs, and discusses emerging strategies to advance bacteria as programmable living therapeutics for cancer treatment.
One-step prepared janus cryogel enables the separation of blood cells and plasma for whole-process hemostasis and accelerated infected wound healing.
Zhang K, Yang H, Sun T … +7 more , Li T, He X, Yu H, Hua J, Yuan MS, Wang J, Tu Q
Biomaterials · 2026 Nov · PMID 42160953 · Publisher ↗
Uncontrolled hemorrhage continues to be a primary cause of clinical mortality. This study presents the synthesis of a Janus Cryogel (SMCP@MS), which integrates rapid hemostatic properties and promotes the healing of infe...
Uncontrolled hemorrhage continues to be a primary cause of clinical mortality. This study presents the synthesis of a Janus Cryogel (SMCP@MS), which integrates rapid hemostatic properties and promotes the healing of infected wounds, targeting three critical stages of hemostasis. The synthesis employs a settling method, whereby silk fibroin (SF) undergoes conformational transformation and separation in a single step, resulting in a bilayer structure. MXene and hydrophobically modified SF spontaneously settle to form a hydrophobic layer. Upon application to bleeding sites, the hydrophobic layer effectively intercepts blood cells, while plasma moves unidirectionally into the material, leading to the separation of plasma from blood cells, which facilitates the second stage of hemostasis by promoting platelet adhesion and thrombus formation. The cross-linked hydrophilic SF forms a macroporous structure with continuous fluid absorption capacity, enabling sustained enrichment of blood components and facilitating the formation of stable fibrin networks, corresponding to the third stage of hemostasis. Furthermore, carbonized typhae pollen (CP) enhances the first stage of hemostasis by expediting vasoconstriction. In an infected wound model, SMCP@MS demonstrated a significantly greater efficacy in wound healing compared to commercial dressings, underscoring its high potential as a dressing, particularly for the treatment of non-compressible hemorrhage and traumatic infections.
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