Biomaterials[JOURNAL]
Sun
200 papers
Hypoxia-activated probiotic vesicle coating enables laminar-shear-protective angiogenesis and antibacterial effects in infectious bone defects.
Chen J, Shi S, Shi T … +8 more , Zhong X, Zhou X, Su Z, Li J, Li J, Luo J, He L, Yang J
Biomaterials · 2026 Nov · PMID 42068791 · Publisher ↗
In treating infectious bone defects, bacterial eradication alone is insufficient, as impaired blood perfusion characterized by low fluid shear stress (FSS) hampers angiogenesis, thereby compromising osteogenesis and dela...
In treating infectious bone defects, bacterial eradication alone is insufficient, as impaired blood perfusion characterized by low fluid shear stress (FSS) hampers angiogenesis, thereby compromising osteogenesis and delaying bone repair. Herein, we engineered a low-FSS-activated, pro-angiogenic implant coating with antibacterial properties. This coating comprises a Fe-tannic acid (Fe-TA) chelation network as the adhesive sublayer, anchoring black phosphorus (BP) nanosheets preloaded with metformin (Met), and is further capped by an outer layer of Lactobacillus animalis-derived extracellular vesicles (BEVs). The Fe-TA and BP components synergistically provide photothermal and photodynamic antibacterial activity, while the BEV layer promotes M2 macrophage polarization and modulates the sustained release of Met and phosphate ions from BP degradation, fostering a pro-regenerative microenvironment. Simultaneously, the BP-mediated photodynamic effect exacerbates local oxygen consumption, amplifying the angiogenic potential of Met under hypoxia. The hypoxia-activated Met lowers the FSS threshold required to enable a laminar shear-protective endothelial phenotype, even under pathological low-FSS conditions. This process drives orderly angiogenesis, restores microvascular perfusion, and supports downstream osteogenesis. Overall, this bioinspired coating integrates "hypoxia activation, vascular guidance, and laminar-flow protection" to promote angiogenesis and osteogenesis, and is augmented by synergistic antimicrobial and immunomodulatory benefits, offering a promising strategy for treating infectious bone defects.
Vitreous humor-mimetic liposomes enable effective gene delivery to the eye via intravitreal injection.
Choi SY, Cho CS, Kim S … +5 more , Kim JH, Kim H, Kim KH, Jo DH, Lee H
Biomaterials · 2026 Nov · PMID 42066435 · Publisher ↗
Inherited retinal disorders such as Norrie disease lack effective therapies, largely owing to the challenges of delivering genes to retinal tissues via intravitreal injection. The efficacy of gene delivery is constrained...
Inherited retinal disorders such as Norrie disease lack effective therapies, largely owing to the challenges of delivering genes to retinal tissues via intravitreal injection. The efficacy of gene delivery is constrained by physical impediments, including the inner limiting membrane and the viscoelastic characteristics of the vitreous humor. In this study, we present the development of vitreous humor-mimetic liposomes (VMLs), which have been shown to facilitate efficient retinal gene delivery by enhancing biocompatibility and tissue absorption. The VMLs were engineered by reproducing the lipidomic composition of the native vitreous, as identified through liquid chromatography-mass spectrometry analysis. The subretinal injection of VMLs was conducted to assess the efficiency of gene expression delivery by VMLs. Notably, VML #3 demonstrated a 1.3-fold enhanced GFP transfection compared to conventional nanoparticle, Lipofectamine 2000. Following intravitreal administration, VML #3 facilitated efficient delivery of pGFP-NDP (Norrie disease protein) plasmids and restored retinal vascularization in both Ndp-hemizygous and oxygen-induced retinopathy mouse models. The findings demonstrate the potential of tissue-inspired nanocarriers as effective platforms for enhancing intraocular delivery, suggesting a clinically applicable strategy for the treatment of inherited retinal diseases, including Norrie disease.
Physiologically relevant 3D tumor models for therapeutic screening.
Xie R, Yang J, Lu X … +5 more , Liu F, Dey M, Kaur N, Peng W, Ozbolat IT
Biomaterials · 2026 Nov · PMID 42066434 · Publisher ↗
The heterogeneity of the tumor microenvironment poses a significant challenge to the success of anti-cancer therapeutics. Consequently, there is an urgent need to generate comprehensive data to elucidate the mechanisms u...
The heterogeneity of the tumor microenvironment poses a significant challenge to the success of anti-cancer therapeutics. Consequently, there is an urgent need to generate comprehensive data to elucidate the mechanisms underlying tumor resistance and to inform the rational and systematic application of anti-cancer drugs to mitigate drug resistance. In-vitro tumor models based on established cell lines are widely employed in studying the mechanisms of action of drugs; however, these traditional models often fail to accurately recapitulate the complexity of native tumors, particularly in terms of the heterogenous and intricate tumor microenvironment, including cellular composition, intercellular communication, and interactions between cells and extracellular matrix. As a result, preclinical data often diverges from clinical outcomes. In recent years, the emergence of patient-derived three-dimensional (3D) models including spheroids, organoids, tumor-on-a-chip systems, and 3D bioprinting has offered promising alternatives for addressing these limitations and enhancing the predictive power of tumor drug screening. In this review, we explore the relationship between the complexity of the tumor microenvironment, tumor drug resistance, and then introduce the current biofabrication techniques enabling the reconstruction of 3D tumor models in vitro. We delve deeper into a myriad of applications of such models for a wide range of cancer indications. These models offer a morfailures andlly relevant platform for evaluating anti-cancer drugs with the potential to improve translational accuracy, reduce drug development failures, and accelerate the discovery of cancer therapies.
Microfluidic pulp platform with vascular integration to evaluate biofunctional material.
Lee MY, Mangal U, Yoon HW … +4 more , Im H, Choi SH, Kwon JS, Shin SJ
Biomaterials · 2026 Nov · PMID 42066433 · Publisher ↗
Biofunctional materials are increasingly used to preserve tooth vitality by promoting dental pulp-mediated hard tissue formation. However, existing evaluation platforms, such as conventional in vitro assays or microfluid...
Biofunctional materials are increasingly used to preserve tooth vitality by promoting dental pulp-mediated hard tissue formation. However, existing evaluation platforms, such as conventional in vitro assays or microfluidic systems, fail to replicate the complex histological and physiological characteristics of dental pulp. This study introduces a 4D biofunctional material-to-pulp (4D BFP) platform that recapitulates pulp physiology, integrating three key features of native pulp tissue: layered histoarchitecture, microcirculatory dynamics, and three-dimensional multicellular organization. This platform further incorporates a temporal dimension by simulating age-dependent vascular transitions, thereby enabling the age-specific modelling of pulp responses, and defining the system as a 4D microfluidic pulp model. Computational fluid dynamics confirmed physiologically relevant flow profiles, while the compartmentalized design supported the spatially organized co-culture of endothelial cell (EC) and human dental pulp stem cell (hDPSC) spheroids. Functional responses to biofunctional material were assessed in both young and mature 4D pulp models. Transcriptomic profiling revealed distinct age- and material-specific signatures related to cellular growth arrest, angiogenesis, and developmental pathways. Collectively, the 4D BFP platform provides a physiological and temporal biomimetic model to study biomaterial-dental pulp interactions, supporting its application as a primary screening tool for candidate biofunctional materials.
Ferroptosis-STING co-activation drives GzmBCD38CD8 T-cell expansion to overcome lymphoma immunosuppression.
Zhu X, Zhang D, Zhang J … +5 more , Fang Z, Zhang Y, Jiang C, Xu R, Hu X
Biomaterials · 2026 Nov · PMID 42061111 · Publisher ↗
The immunosuppressive tumor microenvironment (TME) of B-cell lymphoma limits the efficacy of conventional chemotherapy and hampers the full activation of antitumor immunity. Here, we report a tumor cell membrane-camoufla...
The immunosuppressive tumor microenvironment (TME) of B-cell lymphoma limits the efficacy of conventional chemotherapy and hampers the full activation of antitumor immunity. Here, we report a tumor cell membrane-camouflaged nanoplatform (CM@HFeS/DOX/MSA-2) that couples ferroptosis amplification with cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation to overcome these barriers. The HFeS nanozyme promotes lipid peroxidation (LPO) and reactive oxygen species (ROS) generation, while doxorubicin (DOX) augments immunogenic cell death (ICD) and facilitates cytosolic DNA accumulation, thereby potentiating MSA-2-mediated STING activation. In vitro and in vivo, CM@HFeS/DOX/MSA-2 synergistically induces ferroptosis, enhances ICD hallmarks, and drives robust dendritic cell (DC) maturation. In an A20 B-cell lymphoma model, this biomimetic nanoplatform markedly suppresses tumor growth, increases intratumoral CD8 T-cell and DC infiltration, and reduces immunosuppressive macrophages. Imaging mass cytometry and transcriptomic profiling further identify granzyme B (GzmB)CD38CD8T cells and major histocompatibility complex class II (MHCII)CD103 CD4T cells as key effector populations within the remodeled TME. Immune cell depletion experiments support a critical role for CD8 T cells and the DC-associated immune axis in mediating therapeutic efficacy. Moreover, CM@HFeS/DOX/MSA-2 sensitizes tumors to anti-programmed cell death protein 1 (PD-1) checkpoint blockade and confers strong vaccine-like protection in tumor rechallenge models. Together, this study presents a rationally engineered nanoplatform that coordinately activates ferroptosis and cGAS-STING signaling to reprogram the lymphoma immune landscape and achieve robust, durable antitumor immunity.
Local inhibition of glaucomatous mitochondrial dysfunction using an engineered annular sector microneedle.
Huang B, Xu W, Qiu X … +7 more , Ye B, Wan Z, Luo X, Feng B, Xiang S, Nan K, Lin S
Biomaterials · 2026 Nov · PMID 42061110 · Publisher ↗
Mitochondrial dysfunction plays a critical role in glaucomatous trabecular meshwork (TM) degeneration, whereas increasing intracellular nicotinamide adenine dinucleotide (NAD) levels can restore mitochondrial homeostasis...
Mitochondrial dysfunction plays a critical role in glaucomatous trabecular meshwork (TM) degeneration, whereas increasing intracellular nicotinamide adenine dinucleotide (NAD) levels can restore mitochondrial homeostasis, offering therapeutic benefits for glaucoma. We propose that intracellular NAD can be boosted by promoting NAD biosynthesis through the co-delivery of nicotinamide (NAM), an NAD precursor, and the gene encoding nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1), the rate-limiting enzyme for NAD biosynthesis that consumes NAM. To achieve high gene transfection efficiency, the Nmnat1 gene was encapsulated in a multifunctional lipid nanoparticle (Nmnat1-LNPs). The combination of Nmnat1-LNPs and NAM synergistically reversed mitochondrial dysfunction in primary human trabecular meshwork cells (HTMCs) model. We then developed a new annular sector-shaped microneedle patch (AS-MNs), enabling localized delivery of Nmnat1-LNPs and NAM to the TM. Following application, Nmnat1-LNPs and NAM dual-loaded AS-MNs (Dual@AS-MNs) significantly enhanced the bioavailability of both the Nmnat1 gene and NAM in the TM tissue, leading to a marked reduction in intraocular pressure and alleviation of TM fibrosis in a dexamethasone-induced mice model of glaucoma, highlighting its therapeutic potential. This study presents the first development of an annular sector-shaped microneedle patch as a targeted TM drug delivery platform, and offers a promising new combinatorial strategy for glaucoma treatment.
Engineered attenuated probiotic Escherichia coli oral vaccine provides effective protection against monkeypox virus by eliciting specific systemic and mucosal immunity.
Duan H, Shen C, Fu X … +21 more , Yang W, Gao L, Wu Y, Wei Z, Wang J, Ma F, Jia Y, Zhang Y, Gu Q, He C, Wang Y, Liu X, Jiang D, Liao W, Liu Z, Wang W, Song B, Yang Y, Ma W, Li B, Liao Y
Biomaterials · 2026 Nov · PMID 42061109 · Publisher ↗
Currently available mpox vaccines (actually smallpox vaccines) face numerous challenges including supply shortages, limited specificity, and adverse reactions. Given that monkeypox virus (MPXV) transmits through respirat...
Currently available mpox vaccines (actually smallpox vaccines) face numerous challenges including supply shortages, limited specificity, and adverse reactions. Given that monkeypox virus (MPXV) transmits through respiratory (Clade I) and intimate contact (Clade IIb, primarily sexual behavior), developing vaccines capable of eliciting mucosal immunity is crucial for effective mpox prevention. This study developed an oral mpox vaccine, ABMΔEcN, based on attenuated Escherichia coli Nissle 1917 (ΔEcN). This engineered probiotic stably expresses three MPXV antigens (A9R/B6R/M1R) derived from extracellular enveloped and intracellular mature viruses, while tolerating stomach acid and intestinal fluids. The combination of MPXV antigens with ΔEcN's natural adjuvant properties synergistically enhances both innate and adaptive immune responses following oral administration in mice. This regimen elicits robust humoral and cellular immunity at systemic and mucosal sites with immune memory effect. In VACV and MPXV challenge models, ABMΔEcN conferred potent protection across mucosal sites by improving survival, reducing viral loads and mitigating tissue inflammatory damage. Moreover, ABMΔEcN was found to improve gut microbiota dysbiosis in virus-infected mice, indicating an interaction between mucosal immunity and microbiota homeostasis. This study proposes a novel oral vaccine strategy that enhances immune accessibility through a needle-free administration while achieving comprehensive prevention against mpox.
Oral cascade-responsive nanomedicine to disrupt macrophage-neutrophil crosstalk for intestinal barrier repair.
Cheng Y, Wu D, Liu Q … +8 more , Liu Y, Han X, Cao J, Wang Y, Liu Y, Shen Y, Wang Y, Yu Y
Biomaterials · 2026 Oct · PMID 42055479 · Publisher ↗
Intestinal barrier dysfunction underlies inflammatory bowel disease (IBD) and is driven, in part, by pathological crosstalk between macrophages and neutrophils that sustains pro-inflammatory cytokine release and excessiv...
Intestinal barrier dysfunction underlies inflammatory bowel disease (IBD) and is driven, in part, by pathological crosstalk between macrophages and neutrophils that sustains pro-inflammatory cytokine release and excessive formation of neutrophil extracellular trap (NET). In this study, an oral cascade-responsive nanomedicine, PLBD, was developed to co-deliver the prostaglandin D receptor agonist BW245C and the NET scavenger DNase I with precise spatiotemporal control and minimal off-target release. PLBD comprises mucus-penetrating, reactive oxygen species (ROS)-sensitive liposomes (LBD) formulated from DSPE-SeSe-PEG, which co-encapsulate BW245C and DNase I, and a microbiota-degradable pectin shell providing gastrointestinal protection. After oral administration, the pectin coating facilitates colonic accumulation and undergoes microbiota-mediated fermentation, whereas the exposed PEGylated liposomes penetrate the mucus barrier. In the ROS-rich inflammatory microenvironment, cleavage of the Se-Se linker triggers the synchronous release of payloads. Functionally, released BW245C facilitates a functional shift in macrophages toward an anti-inflammatory M2-like state while DNase I degrades dysregulated NETs, interrupting the inflammatory loop. In murine models of intestinal barrier dysfunction, PLBD restores epithelial barrier integrity, reduces bacterial translocation, rebalances gut microbiota, attenuates IBD and systemic inflammation. Together, this work validates macrophage-neutrophil crosstalk as a tractable therapeutic target and provide a safe, orally translatable biomaterials strategy for intestinal barrier repair.
Redox-imbalance amplification via BODIPY sonosensitizer: A cysteine-depleting oxygen-independent strategy for spatiotemporal deep tumor sonodynamic therapy.
Chen M, Zheng L, Wang L … +4 more , Peng X, Quan YY, Huang ZS, Wang L
Biomaterials · 2026 Oct · PMID 42048842 · Publisher ↗
Sonodynamic therapy (SDT) is a non-invasive cancer treatment that uses ultrasound to activate sonosensitizers and generate reactive oxygen species (ROS), offering the distinct advantage of penetrating deep tumor tissues....
Sonodynamic therapy (SDT) is a non-invasive cancer treatment that uses ultrasound to activate sonosensitizers and generate reactive oxygen species (ROS), offering the distinct advantage of penetrating deep tumor tissues. However, SDT efficacy is hindered by tumor hypoxia and strong antioxidant defenses. Glutathione (GSH), the central ROS scavenger, depends on cysteine (Cys) for synthesis, and tumor cells elevate Cys uptake to preserve redox balance and counter oxidative stress, thereby weakening SDT responsiveness. To address these challenges, we present a multifunctional nanoplatform, NBD-B-T/TiO@Lip, integrating organic and inorganic sonosensitizers within liposomes to optimize solubility, biocompatibility, and ROS production for enhanced sonodynamic therapy. The BODIPY-based NBD-B-T generates oxygen-independent ROS and selectively binds intracellular cysteine, enabling real-time fluorescence imaging while depleting cysteine, disrupting GSH biosynthesis, and perturbing redox homeostasis to trigger ferroptosis. Upon ultrasound activation, the platform synergistically amplifies ROS generation and cysteine depletion, intensifying oxidative stress and ferroptotic cell death in the tumor microenvironment. In vivo, it achieves potent tumor suppression, durable therapeutic efficacy, and minimal systemic toxicity. This strategy establishes a precise, high-efficacy SDT paradigm by uniting oxygen-independent ROS production with targeted redox modulation.
Physiological respiration pressure-driven piezocatalytic therapy for malignant ascites with a gold-core magnified mesoporous piezoelectric nanoplatform.
Zhao Y, Xu Z, Tang L … +14 more , Huang L, Chen M, Xu T, Li S, Sun T, Song L, Luo Y, Yu X, Bian C, Li J, Ma Y, Shi H, Lin Y, He X
Biomaterials · 2026 Oct · PMID 42035586 · Publisher ↗
Malignant ascites (MA), a life-threatening complication of advanced intra-abdominal cancers, poses a formidable clinical challenge due to its complex pathophysiology and the scarcity of effective, low-toxicity treatments...
Malignant ascites (MA), a life-threatening complication of advanced intra-abdominal cancers, poses a formidable clinical challenge due to its complex pathophysiology and the scarcity of effective, low-toxicity treatments. Here, we developed an intelligent respiratory pressure-responsive piezoelectric nanoplatform with a multilayer metal@mesoporous TiO@mesoporous BaTiO architecture (MTB) for piezoelectric therapy of MA. By integrating a metal-TiO Schottky junction and a TiO-BaTiO heterojunction into a mesoporous sandwich configuration, the nanoplatform achieves amplified polarization and suppressed charge recombination, thereby enabling efficient piezocatalytic activation driven by subtle intraperitoneal pressure oscillations from physiological diaphragmatic respiration. Systematic core screening identifies Au@mesoporous TiO@mesoporous BaTiO (AuTB) as the optimal configuration, exhibiting superior piezoelectric responsiveness and reactive oxygen species (ROS) generation capability. Under the mild intra-abdominal pressure oscillations stimulation, AuTB efficiently produces ROS and induces immunogenic cell death (ICD) in tumor cells. In murine MA models, intraperitoneal administration of AuTB markedly suppresses tumor progression, reduces ascites accumulation, and significantly prolongs survival. Mechanistic studies reveal that AuTB-mediated piezocatalysis remodels the immunosuppressive microenvironment by promoting dendritic cell maturation, enhancing cytotoxic CD8 T-cell activation, and reducing regulatory T cells and myeloid-derived suppressor cells. In conclusion, our work establishes a physiologically piezoelectric paradigm that converts endogenous respiratory mechanical energy into sustained antitumor activity, providing a promising translational nanotherapeutic strategy for MA.
Sequential bioelectric programming of Macrophages via ferroelectric nanostructured surface to combat implant infection and promote bone integration.
Li K, Xu Z, Wang X … +7 more , Xu W, Chen Y, Liu X, Wang W, Ge S, Liu H, Li J
Biomaterials · 2026 Oct · PMID 42035585 · Publisher ↗
Implant-associated infections impair osseointegration by suppressing macrophage-mediated antibacterial responses and blocking reparative phenotype transition, while conventional antimicrobial strategies may compromise bo...
Implant-associated infections impair osseointegration by suppressing macrophage-mediated antibacterial responses and blocking reparative phenotype transition, while conventional antimicrobial strategies may compromise bone regeneration. Although electrical stimulation holds promise for macrophage modulation, achieving spatiotemporally controlled bioelectrical regulation remains a challenge. Herein, we engineered a ferroelectric barium titanate-nanostructured titanium implant (ferroTi) that enables sequentially controlled electrical manipulation of macrophages for coordinated antibacterial action and osteogenic promotion. Under ultrasound (US) activation, ferroTi generates dynamic electrical signals (ES) which activate voltage-gated Ca channels to potentiate bacterial phagocytosis in macrophages, eradicating the methicillin-resistant Staphylococcus aureus (MRSA) infection. Concurrently, ferroTi's inherent surface potential provides static electrical signals (ES) that enhance focal adhesion of macrophages and polarize macrophages toward an anti-inflammatory phenotype to foster bone mesenchymal stem cell osteogenesis. In vivo, ferroTi successively eliminated MRSA infection via US-activated ES and significantly enhanced bone integration through ES-driven immunomodulation. This ferroelectric biointerface-mediated immunomodulation presents a synchronized noninvasive strategy for treating infected implants.
Ferroptosis targeted metal-phenolic nanocomposite hydrogel for immune microenvironment guided regeneration of diabetic bone defects.
Hao Y, Zhang Y, Sun J … +9 more , Wang L, Yang H, Huang Z, Liu J, Cheng Q, Cui J, Liu X, Gao Z, Zhang P
Biomaterials · 2026 Oct · PMID 42033991 · Publisher ↗
Diabetic bone defects are not merely a consequence of impaired bone formation, but a complex syndrome driven by chronic hyperglycemia, characterized by dysregulated bone metabolism, vascular impairment, immune imbalance,...
Diabetic bone defects are not merely a consequence of impaired bone formation, but a complex syndrome driven by chronic hyperglycemia, characterized by dysregulated bone metabolism, vascular impairment, immune imbalance, and notably, aberrant activation of ferroptosis in osteoblasts. These multifaceted pathologies pose a major challenge in orthopedic treatment. In this study, we report the development of a metal-polyphenol synergistic hydrogel platform (HES) designed to address the unique demands of diabetic bone regeneration. Epigallocatechin gallate (EGCG) and strontium ions (Sr) are self-assembled into bioactive metal-phenolic network (MPN) nanoparticles (EGCG-Sr NPs), which are uniformly integrated into a three-dimensional hyaluronic acid (HA) hydrogel matrix. This platform achieves spatiotemporal coordination of EGCG-mediated antioxidation and Sr-driven angiogenesis, while EGCG chelates metal ions to inhibit ferroptosis by scavenging ROS, sequestering Fe, protecting GPX4, upregulating HO-1, and suppressing lipid peroxidation. Additionally, EGCG exerts anti-inflammatory effects, and Sr promotes angiogenesis, collectively enhancing osteogenic differentiation and tissue repair. Overall, this multifunctional hydrogel integrates ferroptosis inhibition, antioxidation, immunomodulation, and osteoinduction, offering a promising therapeutic strategy for effective repair of diabetic bone defects.
Oxygen vacancy-rich nanosystems eradicate stubborn periodontal biofilms by synergistic EPS degradation, metabolic activation and microbiome restoration.
Wu Q, You J, Li D … +4 more , Tang S, Wu S, Wang Q, Teng W
Biomaterials · 2026 Oct · PMID 42033990 · Publisher ↗
Periodontitis-associated biofilms pose a severe public health threat due to a dual defense mechanism. This involves a protective physical matrix barrier and biological interference from persistent bacteria and microbial...
Periodontitis-associated biofilms pose a severe public health threat due to a dual defense mechanism. This involves a protective physical matrix barrier and biological interference from persistent bacteria and microbial dysbiosis. Current strategies often fail to penetrate deeply, eradicate dormant persisters and resolve microbial dysbiosis, leading to biofilm resistance and disease recurrence. In this study, we develop a multifunctional nanoplatform combining photothermal, photodynamic therapy and peroxidase-like catalysis to execute a sequential strategy. This system integrates molybdenum oxide nanodots rich in oxygen vacancy (MoO) with the photosensitizer indocyanine green (ICG). It exhibits improved optical and enzymatic performance due to the introduced oxygen vacancies. Upon irradiation, the system produces localized hyperthermia and ROS storms to destabilize the biofilm matrix and promote ultrasmall nanodots penetration. The thermal and oxidative stress increase membrane permeability and reactivate metabolism of dormant persisters. Metagenomic analyses confirms that MoO/ICG-treated biofilms show decreased abundance of key persistence-related genes and great enrichment in metabolic pathways. Additionally, the platform exhibits therapeutic effects and a successful shift towards a healthier oral microbiota in periodontitis model. Overall, MoO/ICG demonstrates excellent biofilm eradication and successfully prevents biofilm regrowth or secondary infection. This work targets the entire biofilm lifecycle and presents a nanoplatform for long-term management of periodontal infections.
High-biocompatibility chitosan-based vectors for high-dose gene therapy in tumor suppression and wound healing.
Shao M, Niu M, Liu Q … +5 more , Sui D, Zhang K, Lian R, Hu Y, Xu FJ
Biomaterials · 2026 Oct · PMID 42033989 · Publisher ↗
The clinical translation of nucleic acid delivery systems demands the development of vectors that are not only efficient but also amenable to scalable production and safe for high-dose administration. Herein, we report a...
The clinical translation of nucleic acid delivery systems demands the development of vectors that are not only efficient but also amenable to scalable production and safe for high-dose administration. Herein, we report a quaternary ammonium chitosan derivative (QCS) synthesized via a straightforward and scalable one-step amine-epoxy ring-opening reaction. This modification enhanced QCS's water solubility, DNA condensation capability and proton buffering capacity, facilitating efficient endo/lysosome escape. The optimal QCS3 formulation achieved transfection efficiency comparable to polyethyleneimine (PEI) but with dramatically reduced cytotoxicity and exceptional hemocompatibility. This superior safety profile enabled high-dose intravenous gene delivery, a regime severely limited by the toxicity of standard cationic polymers like PEI. In tumor-bearing mice, QCS3-mediated delivery of high-dose p53 plasmid effectively suppressed tumor growth, outperforming PEI, which was constrained to low, sub-therapeutic doses. Furthermore, leveraging the same QCS3 platform without modification, delivery of a plasmid encoding growth factor in a rat skin-defect model accelerated wound healing through robust endogenous factor expression. This work highlights QCS as a safe, efficient, and multifunctional gene delivery platform with high clinical potential for diverse applications.
Defect-engineered metal-organic framework as a universal platform for theranostic applications.
Yang S, Xiong X, Zhong Q … +6 more , Xian S, Jiang Y, Hou Y, Xiao Z, Xiao H, Shuai X
Biomaterials · 2026 Oct · PMID 42033988 · Publisher ↗
Rational design of nanocarriers as specific multidrug co-delivery systems to overcome the complex disease microenvironment still remains a critical challenge in precision nanomedicine. In this study, using dicarboxyl-fun...
Rational design of nanocarriers as specific multidrug co-delivery systems to overcome the complex disease microenvironment still remains a critical challenge in precision nanomedicine. In this study, using dicarboxyl-functionalized indocyanine green (Bis-COOH-ICG) as an auxiliary ligand coordinated with Zr clusters, a defect-engineered and functionalized metal-organic framework (Fun-MOF) with hierarchically micro/mesoporous architectures was successfully developed for tumor photothermal/photodynamic combination therapy (PTT/PDT) as well as photoacoustic/fluorescence dual-modal imaging (PAI/FI). And, the hierarchical Fun-MOF enables efficient co-encapsulation of HSP90 inhibitor 17-AAG and catalase (CAT), thus receiving potent antitumor therapy by inhibiting HSP90 overexpression and scavenging hydrogen peroxide to remodel the hypoxic tumor microenvironment. Additionally, owing to the robust coordination chemistry between Zr clusters and carboxyl groups, the defective Fun-MOF also can incorporate other carboxyl-containing small-molecule therapeutics during MOF preparation, making it a universal platform for diverse theranostic applications.
MOF nanosheets with topology enhanced ultrahigh relaxivity.
You Y, Wu W, Zhou X … +9 more , Liu H, Zheng X, Lu L, Yin H, Yin J, Zhang N, Tao J, Lin B, Zhao P
Biomaterials · 2026 Oct · PMID 42025046 · Publisher ↗
Two-dimensional (2D) metal-organic framework (MOF) nanosheets have emerged as a promising class of functional materials. Nevertheless, the fabrication of MOF nanosheets with well-defined uniformity and ultrathin thicknes...
Two-dimensional (2D) metal-organic framework (MOF) nanosheets have emerged as a promising class of functional materials. Nevertheless, the fabrication of MOF nanosheets with well-defined uniformity and ultrathin thickness via traditional synthetic strategies still remains a great challenge. Herein, we report that ultrasonic treatment plays a crucial regulatory role in the bottom-up assembly of MOF nanosheets. This innovative synthetic protocol enables the precise preparation of Co-Mn-TCPP nanosheets with a uniform thickness of ∼1.82 nm. Notably, the as-synthesized Co-Mn-TCPP nanosheets exhibit an ultrahigh longitudinal relaxivity (r) of 12.05 mMs. A combination of theoretical calculations and experimental characterizations reveals that the exceptional relaxivity of Co-Mn-TCPP nanosheets stems predominantly from their unique 2D square lattice structure, which imposes a strong restriction on molecular motion and thus prolongs the rotational correlation time (τᵣ). Furthermore, this single-unit-cell 2D MOF demonstrates remarkable magnetic resonance imaging (MRI) contrast enhancement efficacy across multiple tumor models. More importantly, it can effectively assist in MRI-guided precise resection of small tumors. This work not only showcases the great versatility of ultrasound as a powerful tool for the synthesis of high-quality MOF nanosheets but also provides a new strategy for the design of high-relaxivity MRI contrast agents by capitalizing on specific 2D topological features.
Catch and light up: Dual bioorthogonal reactions actualize fluorescent probe retention and activation for surgical navigation.
Ding M, Li H, Yang W … +5 more , Ullah I, Chen Z, Liu Y, Wang K, Yuan Y
Biomaterials · 2026 Oct · PMID 42025045 · Publisher ↗
Fluorescent molecular probes are promising imaging tools for tumor surgical navigation. However, achieving both precise diagnosis and long-term surgical navigation in complex tumor environments remains challenging. In th...
Fluorescent molecular probes are promising imaging tools for tumor surgical navigation. However, achieving both precise diagnosis and long-term surgical navigation in complex tumor environments remains challenging. In this study, we developed a "catch and light-up" fluorescent probe (CyTB) that enables specific fluorescence retention and activation, thereby enhancing imaging navigation accuracy. The probe consists of a hemicyanine unit as the near-infrared fluorescence signal reporter, tetrazine (Tz) reactive group bicyclo [6.1.0]nonyne (BCN) and trans-cyclooctene (TCO). Once arrival at the tumor site labeled by Tz in advance, the BCN group of probes was anchored through ligation reaction to enhance the probe retention. Concurrently, the TCO group can rapidly be cleaved by Tz leading to the light-up of fluorescence. The retention time of the probe at the tumor site can reach 130 h, while the tumor-to-normal tissue ratio in metastatic microtumor of pancreatic cancer (< 2 mm) still reaches 6.5, enabling efficient tumor tracking and precise marginal resection, thus providing a promising strategy for surgical navigation.
Selective induction of mitochondrial fragmentation for cancer immunotherapy via mtDNA-Targeting AIE photosensitizer.
Wang WJ, Hao YX, Wang YM … +8 more , Xin ZY, Zhang M, Xin HT, Feng J, Li K, Zhao Z, Tang BZ, Wang KN
Biomaterials · 2026 Oct · PMID 42025044 · Publisher ↗
Mitochondrial damage in tumor cells has recently emerged as a mechanism of immunogenic cell death, with precise triggers acting as potent antitumor immunostimulants. Here, we developed PyTPAMa, an asymmetric AIE-active p...
Mitochondrial damage in tumor cells has recently emerged as a mechanism of immunogenic cell death, with precise triggers acting as potent antitumor immunostimulants. Here, we developed PyTPAMa, an asymmetric AIE-active photosensitizer that selectively accumulates in mitochondria and binds mitochondrial DNA (mtDNA) and induces mitochondrial fragmentation to trigger strong immunostimulation. Upon light activation, PyTPAMa generates a spatially confined, hybrid Type I/II ROS burst that disrupts the mitochondrial network, causing mitochondrial fragmentation, opening the mitochondrial permeability transition pore, and releasing mtDNA into the cytosol. This activates the NLRP3-GSDMD inflammasome, initiating pyroptosis and orchestrating systemic antitumor immunity. RNA sequencing reveals widespread silencing of mitochondrial genes and reprogramming of the NLRP3 inflammasome and antigen-presentation pathways. As a programmable immune ignition switch, PyTPAMa induces immunogenic cell death in vitro, transforms distant "cold" tumors into immune-infiltrated lesions in vivo, and achieves 96% suppression of bilateral 4T1 tumors without systemic toxicity. This work establishes mitochondrial fragmentation as a programmable immune switch and validates PyTPAMa for fragmentation-driven cancer immunotherapy.
Interventional therapy for hepatocellular carcinoma in the immunotherapy era: From mechanism exploration to materials innovation.
Tang B, Yang J, Xu W … +10 more , Wang G, Ye W, Li C, Wan J, Zhou Y, Yu C, Jin C, Yan Z, Qu X, Zhang W
Biomaterials · 2026 Oct · PMID 42008884 · Publisher ↗
Hepatocellular carcinoma(HCC) ranks among the leading causes of cancer-related mortality worldwide. In the treatment landscape of HCC, transarterial therapies plfan'yiay a crucial role. This review focuses on transarteri...
Hepatocellular carcinoma(HCC) ranks among the leading causes of cancer-related mortality worldwide. In the treatment landscape of HCC, transarterial therapies plfan'yiay a crucial role. This review focuses on transarterial embolization for HCC, with particular emphasis on transarterial chemoembolization(TACE) and transarterial radioembolization(TARE), exploring their significant effects on the tumor microenvironment. TACE involves the liberation of tumor-derived antigens and damage-associated molecular patterns (DAMPs), while exerting direct modulatory influences on immune populations including tumor-infiltrating macrophages, cytotoxic T cells, and natural killer lymphocytes. This process, in turn, activates the local immune response while simultaneously inducing changes in the tumor's vascular environment. These changes have unveiled novel opportunities for immunotherapy and targeted therapy. Additionally, nanomaterials have emerged as a significant component in both HCC treatment and TACE therapy. Their unique properties facilitate improved drug delivery, precise modulation of the immune microenvironment, and ultimately, better treatment outcomes. They can targetedly ameliorate the hypoxic and acidic immunosuppressive tumor microenvironment. Furthermore, by activating immunogenic cell death and regulating immune cell infiltration, these materials can reverse immunosuppression. Looking ahead, elucidating the intricate mechanisms by which TACE modulates the immuno-tumor microenvironment and developing innovative therapeutics that specifically target the tumor microenvironment will remain key focal points in future HCC research.
On-demand recession of quaternary ammonium biocides for combating multidrug resistance.
Han W, Cheng X, Luo Y … +4 more , Ma A, Xu XQ, Du W, Wang Y
Biomaterials · 2026 Oct · PMID 42008883 · Publisher ↗
Antibiotic misuse is a key driver of antimicrobial resistance, but extensive use and prolonged environmental persistance of disinfectants like quaternary ammonium compounds (QACs), poses an urgent and underappreciated th...
Antibiotic misuse is a key driver of antimicrobial resistance, but extensive use and prolonged environmental persistance of disinfectants like quaternary ammonium compounds (QACs), poses an urgent and underappreciated threat. Conventional QACs accumulate at sub-inhibitory concentrations (sub-MICs), accelerating multidrug resistance (MDR) in bacteria via sustained selection pressure. We introduce R-substituted silaketal-bridged QACs (RSBQs), which feature acid-cleavable linkages that enable controllable hydrolysis from bactericidal to non-toxic states. By modulating the R-substituents and environmental conditions, degradation half-lives range from 12 h to 6 days, reducing selection pressure before resistance establishes. Even at sub-MICs, partially degraded RSBQs such as ethyl-substituted SBQ (Et-SBQ) and n-propyl-substituted SBQ (nPr-SBQ), exhibit dual resistance-suppression, including downregulation of resistance gene expression and inhibition of efflux pump activity. By resensitizing multidrug-resistant bacteria to antibiotics, Et-SBQ synergized with ciprofloxacin to accelerate wound healing in mice. This strategy combines potent antibacterial activity, environmental degradability, and resistance suppression, offering a promising MDR solution.
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