Biomaterials[JOURNAL]
Sun
200 papers
Opposing intracellular redox modulation by a carrier-free diselenide nanosystem integrates antifibrosis and ferroptosis sensitization for fibrotic pancreatic cancer therapy.
Xue Y, Zheng Q, Luo Y … +8 more , Chen M, Li J, Xiong D, Li M, Chen Y, Li X, Liu J, Hou Y
Biomaterials · 2026 Jun · PMID 42361749 · Publisher ↗
The excessive fibrosis and immunosuppression characteristic of pancreatic ductal adenocarcinoma (PDAC) necessitate multi-targeted tumor microenvironment (TME) regulation. Multi-functional integration in these platforms r...
The excessive fibrosis and immunosuppression characteristic of pancreatic ductal adenocarcinoma (PDAC) necessitate multi-targeted tumor microenvironment (TME) regulation. Multi-functional integration in these platforms raises preparation, stability and biosafety concerns, whereas structurally simple materials that enable equivalent TME modulation provide a streamlined solution. Herein, we report a carrier-free system (C8DSe) constructed solely from diselenide. Iron-free C8DSe effectively induces oxidative stress to trigger ferroptosis in tumor cells, while reversing TGF-β induced NIH-3T3 cells activation through simultaneous targeting of the TGF-β/Smad and antioxidant non-canonical NRF2-ARE pathways. It overcomes activated NIH-3T3 cells-mediated ferroptosis resistance by increasing ferrous ion content, inhibiting antioxidant systems, and promoting lipid peroxidation. In orthotopic fibrotic PDAC models, C8DSe exhibits potent antitumor efficacy through direct cytotoxicity, fibrosis reduction, and immune activation. These findings establish diselenide as multi-target agent for TME regulation, providing a template for single-compound therapies and advancing diselenide-based therapeutics.
Dissolving microneedle array size influences physical adjuvanticity for dose-sparing vaccination.
Min HS, Lee Y, Cho SM … +6 more , Park S, Nam J, Oh HI, Kim P, Shin JH, Jung H
Biomaterials · 2026 Jun · PMID 42361748 · Publisher ↗
Dissolving microneedles (DMNs) are an emerging biomaterial platform for transdermal vaccination, enabling precise antigen delivery into antigen-presenting cell-rich skin layers. Here, we identify a previously underapprec...
Dissolving microneedles (DMNs) are an emerging biomaterial platform for transdermal vaccination, enabling precise antigen delivery into antigen-presenting cell-rich skin layers. Here, we identify a previously underappreciated size dependent immunomodulatory biomaterial function of DMNs: their ability to act as physical adjuvants through controlled tissue micro-injury. Microneedle insertion generates spatially distributed and transient skin micro-injury that induces the release of damage-associated molecular patterns, prominently high-mobility group box 1 (HMGB-1), thereby establishing a localized inflammatory field that bridges mechanical input to immune activation. Importantly, the magnitude of this response is quantitatively governed by microneedle array size, revealing device architecture as a tunable design parameter for modulating biological outcomes. Array size-dependent micro-injury promoted dendritic cell activation and lymphatic trafficking, resulting in enhanced humoral responses, including elevated antigen-specific IgG titers and increased plasma cell frequencies, even in the absence of exogenous adjuvants. Despite robust innate activation, DMN-induced inflammation was localized and fully resolved within one week, demonstrating favorable tissue compatibility. Collectively, these findings establish microneedle array design as a controllable biomaterial-based strategy to program physical adjuvanticity, enabling safe, adjuvant-free, and dose-sparing vaccination.
Spark plasma sintered titania-graphene oxide: A toothless keratoprosthesis for end-stage corneal blindness.
Ng S, Torresani E, Han E … +13 more , Wong YR, Soo JYW, Ong HS, Abusayf MM, Look Z, Catbagan K, Barathi VA, Olevsky EA, Low T, Goh BT, Khor KA, Mehta JS, Riau AK
Biomaterials · 2026 Jun · PMID 42361747 · Publisher ↗
The osteo-odonto keratoprosthesis (OOKP) remains a groundbreaking treatment for end-stage corneal blindness after 50 years, but is surgically complex and unsuitable for certain patients, particularly those without health...
The osteo-odonto keratoprosthesis (OOKP) remains a groundbreaking treatment for end-stage corneal blindness after 50 years, but is surgically complex and unsuitable for certain patients, particularly those without healthy teeth. We developed a novel keratoprosthesis (KPro) comprising spark plasma sintered titania-graphene oxide (TiGO) and a 5-mm PMMA optical cylinder, and evaluated its performance as an alternative to the tooth in the OOKP. The KPro's suitability for implantation was first demonstrated through the preservation of surface integrity, chemical structure, and mechanical strength following ethylene oxide sterilization. Mechanical pull-out tests showed that PMMA adhered more strongly to TiGO than to primate teeth after bonding with dental cement, suggesting that the same cement used in OOKP procedures can be used with TiGO skirts. In addition, in vitro studies confirmed TiGO's biocompatibility, supporting adhesion, proliferation, and viability of human corneal stromal fibroblasts. In a rabbit model of OOKP stage 1 surgery, the TiGO integrated successfully into dermal tissue, showing vascularized connective tissue with positive staining for collagen I and III and CD31. In stage 2 simulation, implantation of fibrovascularized KPro onto the ocular surface, under the nictitating membrane, was uneventful with no evidence of tissue melt, PMMA detachment, or adverse inflammatory response over six months. Immunohistological analysis showed that fibrovascular and immune cell markers in the implanted eyes were highest in the nictitating membrane proximal to the PMMA optical cylinder, decreased toward the distal regions, and were low throughout the host cornea. In conclusion, our TiGO-based KPro offers a promising alternative to OOKP, with advantages including a larger PMMA optical cylinder, less complex surgery, and broader surgical indications.
Programmable multivalent aptamer-drug conjugates enable stable tumor targeting and enhanced therapy for advanced bladder cancer.
Tao S, Zhong Y, Ju J … +7 more , Sun X, Guo B, Xia Q, Chen H, Tian T, Tan W, Lei H
Biomaterials · 2026 Jun · PMID 42361746 · Publisher ↗
The therapeutic potential of aptamer-drug conjugates (APDCs) is constrained by challenges in achieving high in vivo stability, strong target affinity, and binding robustness under blood flow-induced mechanical stress. To...
The therapeutic potential of aptamer-drug conjugates (APDCs) is constrained by challenges in achieving high in vivo stability, strong target affinity, and binding robustness under blood flow-induced mechanical stress. To address these limitations, multivalent APDCs have been actively explored; however, most reported designs rely on heterogeneous assemblies, and their binding stability under mechanical perturbations remains poorly characterized. Here, we report a programmable and structurally defined multivalent APDC, termed Multi-MMAE, constructed via hybridization chain reaction (HCR)-mediated DNA assembly. This architecture enables tunable modulation of aptamer multivalency and drug incorporation, allowing multivalent presentation of both the PTK7-targeting aptamer Sgc-8 and the cytotoxic payload monomethyl auristatin E via a cleavable VC-PAB linker. Compared with monovalent Sgc-8-MMAE, Multi-MMAE exhibits enhanced serum stability, ∼11.5-fold higher binding affinity, improved binding stability under flow-mimicking perturbations, and increased cellular uptake and intracellular drug delivery. At equivalent MMAE doses, Multi-MMAE demonstrates superior antitumor efficacy and survival benefits in both orthotopic and experimental lung colonization bladder cancer mouse models, accompanied by prolonged circulation, enhanced tumor retention relative to Sgc-8-MMAE, and reduced systemic toxicity compared with free MMAE. Mechanistic studies further reveal that structural multivalency modulates intracellular trafficking pathways and pharmacodynamic behavior. Collectively, this work establishes a modular aptamer-drug conjugate strategy for advancing APDC-mediated cancer therapy.
Neutrophil-hitchhiking nanodrug precisely silences neutrophil activation and rebuilds immune homeostasis in rheumatoid arthritis without compromising host defense.
Zhang G, Hu C, Li B … +5 more , Qian C, Zhang H, Zhang W, Xie D, Deng J
Biomaterials · 2026 Jun · PMID 42349053 · Publisher ↗
Rheumatoid arthritis (RA) is a chronic autoimmune disease, and current antirheumatic drugs have poor efficacy or cause considerable systemic adverse reactions. Neutrophil activation is a central driver of RA pathogenesis...
Rheumatoid arthritis (RA) is a chronic autoimmune disease, and current antirheumatic drugs have poor efficacy or cause considerable systemic adverse reactions. Neutrophil activation is a central driver of RA pathogenesis; however, approaches that curb pathogenic neutrophil activity while preserving host defense are lacking. In patients with RA, we identified spleen tyrosine kinase (SYK) as a key upstream regulator whose aberrant activation drives neutrophil hyperactivation, neutrophil extracellular trap (NET) formation, inflammatory mediator release, and delayed apoptosis, while preserving antimicrobial function. Moreover, we engineered a HSA-AAPV-TKI (HAT) nanodrug by conjugating human serum albumin (HSA) to a SYK-targeted tyrosine kinase inhibitor (TKI) via a neutrophil elastase-cleavable AAPV peptide linker (Ala-Ala-Pro-Val). HAT is preferentially internalized by circulating neutrophils in CIA mice, traffics with them to inflamed joints, and releases the inhibitor in response to local neutrophil activation, thereby attenuating SYK signaling and pathogenic neutrophil functions while largely preserving antimicrobial activity. In a collagen-induced arthritis mouse model, HAT significantly reduced joint swelling, arthritis scores, and structural joint damage without impairing host defense. This strategy establishes a new RA therapeutic avenue that reconciles potent efficacy with immune safety and represents a milestone toward translational neutrophil-targeted therapy.
Neutrophil-hitchhiking and bone-targeting ultrasound-responsive nanomodulators for synergistic immunogenic tumor inhibition and bone repair of bone metastasis.
Hu Z, Chen Z, Liu Y … +2 more , Su T, Li J
Biomaterials · 2026 Jun · PMID 42349052 · Publisher ↗
Bone metastasis, a major contributor to skeletal complications in advanced cancers, poses a significant therapeutic challenge, largely attributable to poor drug delivery, self-perpetuating bone-tumor vicious cycle and se...
Bone metastasis, a major contributor to skeletal complications in advanced cancers, poses a significant therapeutic challenge, largely attributable to poor drug delivery, self-perpetuating bone-tumor vicious cycle and severe bone damages. Herein, we engineered a multifunctional ultrasound (US)-responsive nanomodulator (SPNacs) through the co-assembly of a semiconducting polymer sonosensitizer (PF8DPP) and curcumin (Cur) with a reactive oxygen species (ROS)-cleavable polymer shell containing both bone and neutrophil dual-targeting ligands (alendronate and sialic acid). This design enabled a sequential targeting strategy, in which SPNacs first associated with circulating neutrophils for systemic transport and subsequent homing to bone metastatic niches via neutrophil-hitchhiking recruitment. Upon arrival at the metastatic sites, alendronate on the surface of SPNacs further exerted the second-step bone-targeting effect by chelating hydroxyapatite, thereby enhancing local retention and drug accumulation within the bone metastatic tumor microenvironment. External US irradiation activated this system to trigger the generation of cytotoxic ROS for tumor sonodynamic therapy and concurrently ruptured the ROS-cleavable polymer shell to accelerate the on-site release of Cur. The released Cur exerted as a modulator to alleviate the immunosuppressive state of the tumor microenvironment through downregulating programmed cell death ligand 1 (PD-L1) expression, while the Cur-mediated osteogenic effect combined with ALN-mediated osteoclast inhibition synergistically promoted bone repair. Consequently, a synergistic effect was achieved to simultaneously suppressed tumor progression and fostered bone tissue regeneration. Collectively, this study presents a promising therapeutic strategy that addresses both tumor eradication and skeletal repair within metastatic bone lesions.
Physical continuity at biomaterial-ECM interfaces is associated with reduced fibroblast activation and NF-κB signaling.
Suarez-Arnedo A, Harris M, Robinson C … +5 more , Riley L, Kim A, Zhang L, Hoffman BD, Segura T
Biomaterials · 2026 Jun · PMID 42349051 · Publisher ↗
Fibrotic responses at biomaterial-tissue interfaces limit implant integration and regenerative healing, yet how the interaction between biomaterials and the extracellular matrix (ECM) regulates fibroblast activation rema...
Fibrotic responses at biomaterial-tissue interfaces limit implant integration and regenerative healing, yet how the interaction between biomaterials and the extracellular matrix (ECM) regulates fibroblast activation remains poorly understood. Granular hydrogels including microporous annealed particle (MAP) scaffolds reduce fibrosis, while chemically and mechanically matched hydrogels do not, suggesting a dominant role for scaffold architecture. To determine how biomaterial architecture influences extracellular matrix (ECM) integration and fibroblast activation, we developed a reductionist in vitro model that integrates collagen type I with either MAP scaffolds or chemically and mechanically matched bulk hydrogels. MAP scaffolds allow collagen infiltration and form physically continuous composites, whereas hydrogels exclude collagen and generate interfacial slip planes. This physical integration stabilizes collagen architecture, limits fibroblast-mediated matrix compaction, suppresses contractility, and attenuates myofibroblast transition. Fibroblasts in mechanically integrated environments exhibit reduced expression and nuclear localization of NF-κB and are enriched for quiescent phenotypes. Together, these findings identify biomaterial-ECM physical continuity as a design principle for limiting fibrotic signaling.
Synergistic "targeting and blockade" strategy via engineered exosomes and clinical ultrasound contrast agent for hepatocyte-targeted mRNA delivery.
Li Z, Zhang B, Liu C … +9 more , Wang W, Li G, Xu B, Liu F, Li X, Dong C, Zhao P, Xing C, Yuan L
Biomaterials · 2026 Jun · PMID 42341362 · Publisher ↗
Homozygous familial hypercholesterolemia (HoFH) presents a persistent and difficult-to-treat condition. This recalcitrance stems largely from loss-of-function mutations within the low-density lipoprotein receptor (LDLR)...
Homozygous familial hypercholesterolemia (HoFH) presents a persistent and difficult-to-treat condition. This recalcitrance stems largely from loss-of-function mutations within the low-density lipoprotein receptor (LDLR) gene, which severely undermine the efficacy of standard therapeutic regimens. Here, we report a bioinspired "targeting and blockade" strategy for the efficient delivery of functional Ldlr mRNA to hepatocytes. This approach is realized through a rationally designed platform, Szd + AP@Exo, which integrates APOA1-functionalized exosomes for hepatocyte-targeted delivery with a preemptive macrophage blockade using the clinical ultrasound contrast agent Sonazoid (Szd). The APOA1 modification confers specific recognition by the scavenger receptor class B type 1 on hepatocytes, while the pre-saturation of Kupffer cells with Szd significantly mitigates nonspecific clearance by the mononuclear phagocyte system (MPS). In a HoFH murine model, this synergistic strategy markedly enhanced the accumulation of exosomes in hepatocytes and achieved robust restoration of hepatic LDLR expression. Consequently, it elicited a profound correction of the atherogenic lipid profile and substantially attenuated the progression of atherosclerosis. A comprehensive biosafety evaluation confirmed the excellent biocompatibility of this platform. Our work provides a promising and broadly applicable solution for the treatment of liver-related genetic disorders by simultaneously overcoming the critical barriers of targeted delivery and MPS evasion.
High-precision freeform DLP bioprinting by thermo-reversible gelation.
Han D, Zhang M, Xie J … +10 more , Dong Z, Xia S, Zhan Y, Dong Y, Li Y, Wang J, Deng Z, Mei J, Tian J, Ye Q
Biomaterials · 2026 Jun · PMID 42341361 · Publisher ↗
Light-based 3D bioprinting technology can be used to prepare complex hydrogel structures for tissue engineering, but it is limited by reduced precision due to radical diffusion and light scattering, as well as geometric...
Light-based 3D bioprinting technology can be used to prepare complex hydrogel structures for tissue engineering, but it is limited by reduced precision due to radical diffusion and light scattering, as well as geometric restriction. We propose a reversible gelation suspension stereolithography technique, which combines DLP printing with temperature-controlled reversible gelation, gelling the bioink prior to photocuring. This strategy suppresses diffusion and scattering, achieving 6.8 μm precision, and provides in situ support for suspended structures, overcoming traditional geometric restriction. We demonstrated the feasibility in unrestricted geometry by printing various structures and demonstrated multi-material printing. Cell-loaded hexagonal hepatic lobule bio-inspired structure and multi-scale branched vessels seeded with HUVEC were then constructed, high survival rates and functional performance demonstrated its superior biocompatibility, thereby providing possibilities for new tissue engineering applications.
A pH-responsive liposomal nanoplatform for reprogramming lactate metabolism and immunogenic activation in pancreatic cancer.
Zhang Y, Shen Y, Zhang Z … +16 more , Song M, Zhang J, Zhang Y, Liang J, Wu H, Zhao Y, Zhang Z, Xu S, Han X, Li Y, Guan Z, Liu H, Zou X, Zhang S, Zhang S, Lv Y
Biomaterials · 2026 Jun · PMID 42335581 · Publisher ↗
Pancreatic cancer is characterized by excessive lactate accumulation, which establishes a profoundly immunosuppressive tumor microenvironment (TME) and limits the efficacy of immunotherapy. Here, we identify lactate-driv...
Pancreatic cancer is characterized by excessive lactate accumulation, which establishes a profoundly immunosuppressive tumor microenvironment (TME) and limits the efficacy of immunotherapy. Here, we identify lactate-driven immune suppression as a central barrier to antitumor immunity, which is difficult to effectively modulate in vivo due to poor intratumoral drug delivery, and develop a pH-responsive liposomal nanoplatform (S&P@RL) to simultaneously enhance tumor immunogenicity and relieve metabolic immune suppression. S&P@RL co-delivers Polyphyllin VI (PPVI), which induces pyroptosis, immunogenic cell death (ICD), and STING activation, and Syrosingopine (Syro), an MCT4 inhibitor that blocks lactate efflux. RGD-mediated targeting and acid-labile hydrazone cleavage enable enhanced intratumoral distribution and microenvironment-triggered drug release. In pancreatic cancer models, S&P@RL markedly reduced intratumoral lactate levels, promoted the maturation of dendritic cells (DCs), enhanced CD8 T-cell and natural killer (NK) cell infiltration, and reprogrammed macrophages toward an M1 phenotype while suppressing regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs). Consequently, tumor growth and lung metastasis were significantly inhibited. Notably, S&P@RL sensitized pancreatic cancer to PD-1 blockade, effectively converting immunologically "cold" tumors into "hot" tumors without systemic toxicity. This study establishes a biomaterial-enabled strategy that integrates metabolic reprogramming and immune activation to overcome immune resistance in pancreatic cancer.
Nanozyme-augmented clinical drug strategy for dopaminergic restoration and oxidative stress mitigation to rescue motor and cognitive deficits in Parkinson's disease.
Feng Y, Chen C, Sun J … +12 more , Zhang L, Wang Y, Dai W, Mei B, Wang D, Qiu G, Wang P, Qing X, Yang Z, Zhang J, Liu X, Liu H
Biomaterials · 2026 Jun · PMID 42330585 · Publisher ↗
Current treatments for Parkinson's disease (PD) fail to halt dopaminergic neurodegeneration and remain largely ineffective against cognitive impairment. Here, we developed IP@ALipo, a nanoplatform that co-delivers the cl...
Current treatments for Parkinson's disease (PD) fail to halt dopaminergic neurodegeneration and remain largely ineffective against cognitive impairment. Here, we developed IP@ALipo, a nanoplatform that co-delivers the clinical drug pramipexole (PPX) and PEGylated iron oxide nanozyme particles (PEG-IO) via Angiopep-2-modified liposomes capable of crossing the blood-brain barrier (BBB). In the PD mouse model, in vivo photometry showed that a single dose of IP@ALipo significantly enhanced dopaminergic signaling from the substantia nigra pars compacta (SNc) to the striatum (STr) via its PPX component. Facilitated by PEG-IO in IP@ALipo, repeated administration further suppressed cerebral ROS and promoted sustained dopaminergic recovery, resulting in improved motor function. Importantly, the PEG-IO component also preserved hippocampal neurons and restored synaptic architecture, yielding pronounced cognitive benefits. This study demonstrates a nanozyme-augmented strategy for clinical drugs that not only sustains nigrostriatal dopaminergic recovery but also provides cognitive improvements beyond conventional Parkinson's treatments, offering a comprehensive therapeutic approach.
Ready-to-use, in situ formed collagen/RGD/hyaluronic acid hydrogel: accelerating full-thickness wound healing.
Zheng T, Li S, Li Y … +6 more , Song J, Huang P, Gu X, Yang K, Liu X, Wang X
Biomaterials · 2026 Jun · PMID 42330584 · Publisher ↗
A robust strategy was developed to customize the hydrogel's composition, concentration, and crosslink density, thereby providing a method for the screening and optimization of skin repair hydrogels. Specifically, methylt...
A robust strategy was developed to customize the hydrogel's composition, concentration, and crosslink density, thereby providing a method for the screening and optimization of skin repair hydrogels. Specifically, methyltetrazine-modified collagen (Col-T), norbornene-modified RGD peptide, and norbornene-modified hyaluronic acid with varying degrees of modification (HA-N, HA-N, and HA-N), were synthesized. Upon mixing Col-T, RGD-N, and one of the HA-N derivatives, a bioorthogonal reaction was immediately initiated, thereby forming an in situ crosslinked, shape-adaptable hydrogel. An extracellular matrix-mimetic hydrogel composed of collagen, RGD peptide, and hyaluronic acid was optimized using human epidermal stem cells (hEpdSCs), human dermal fibroblasts (HDFs), and human umbilical vein endothelial cells (HUVECs). The optimized hydrogel effectively promoted the hEpdSCs proliferation, the proliferation and migration of HDFs, and the migration and tubular formation of HUVECs. In comparison, GelMA exhibited significant cytotoxicity against hEpdSCs due to the use of photoinitiator LAP. The hydrogel exhibited anti-hemolytic, pro-coagulant, and tissue-adhesive properties, and significantly accelerated the healing of 15 mm × 15 mm full-thickness wound after a single application without any additives. This hydrogel was associated with enhanced hair follicle-like structure formation and reduced inflammation-related responses in the wound area. Furthermore, its ready-to-use and biodegradable nature made it highly suitable for clinical applications.
Bio-inspired indocyanine green supramolecular assemblies for high-contrast NIR-II imaging and cooperative dual-targeting of bladder cancer.
Xu H, Wu J, Bai Y … +6 more , Qin J, Sun R, Li Z, Tang K, Liu Y, Zhu J
Biomaterials · 2026 Jun · PMID 42323929 · Publisher ↗
Developing supramolecular strategies that simultaneously regulate photophysical behavior and enable efficient biological targeting of indocyanine green (ICG) remains a major challenge for clinically compatible near-infra...
Developing supramolecular strategies that simultaneously regulate photophysical behavior and enable efficient biological targeting of indocyanine green (ICG) remains a major challenge for clinically compatible near-infrared region II (NIR-II) probes, as aggregation-caused quenching and ineffective tumor targeting severely limit their diagnostic potential. Here, inspired by natural light-harvesting complexes that utilize cooperative supramolecular interactions and spatial confinement to regulate chromophore behavior, we report a multi-interaction supramolecular engineering strategy to construct an ICG complex (CMPI) that simultaneously enhances photophysical performance and enables microenvironment-responsive cooperative dual targeting. A β-cyclodextrin-M2pep-aconitic acid carrier establishes a synergistic network of host-guest inclusion, electrostatic attraction, hydrogen bonding, and steric effects, which suppresses aggregation and stabilizes ICG within a spatially confined environment, thereby markedly enhancing NIR-II brightness (∼4-fold) and quantum yield (∼1.9%). In acidic tumor microenvironments, CMPI undergoes rapid charge reversal and in situ assembly, thereby amplifying the targeting of M2-like tumor-associated macrophages. Finally, CMPI prolongs circulation (half-life t ∼14.1 min), preserves the clearance ability of ICG, and achieves a tumor-to-normal ratio of ∼11.1, enabling high-contrast NIR-II imaging and fluorescence-guided surgery across multiple bladder tumor models, including sensitive detection of sub-millimeter lesions. This strategy provides a clinically compatible supramolecular approach for simultaneously enhancing the photophysical properties and targeting of FDA-approved dyes.
A mechanism-inspired integrated dual-frequency ultrasound transducer for cavitation-enhanced transdermal drug delivery.
Zhang Y, Chen Z, Ye K … +7 more , Shang Z, Wu M, Zhao S, Chen Z, Chen X, Xu J, Fei C
Biomaterials · 2026 Jun · PMID 42322803 · Publisher ↗
Ultrasound has gained widespread application in the field of transdermal drug delivery (TDD), including dermatological therapy and aesthetic medicine, owing to its non-invasive nature and cost-effectiveness. Despite its...
Ultrasound has gained widespread application in the field of transdermal drug delivery (TDD), including dermatological therapy and aesthetic medicine, owing to its non-invasive nature and cost-effectiveness. Despite its widespread use, clinical researchers have largely relied on empirical selection of low-frequency ultrasound (tens to hundreds of kHz) for single-frequency sonophoresis, and a mechanistic understanding of how ultrasound frequency regulates cavitation-from nucleation to bubble collapse-remains lacking, which limits the rational design of ultrasound-based TDD systems. In this study, we proposed a simulation framework that couples Zwart-Gerber-Belamri (ZGB) cavitation model (for nucleation) with Keller-Miksis (K-M) equation (for bubble dynamics), thereby addressing the limitation of existing models that treat nucleation and bubble growth/collapse separately. Using this model, we analyzed the relationship between ultrasound frequency and cavitation effects was analyzed. The results indicate that high-frequency ultrasound can facilitate faster generation of more cavitation nuclei, whereas low-frequency ultrasound is more conducive to the growth and collapse of pre-existing bubbles. Based on these findings, an integrated dual-frequency (400 kHz, 2 MHz) ultrasound transducer (iDFUT) was designed and fabricated to enhance the efficacy of dermatological treatments. Both in vitro and in vivo studies confirmed that this device significantly improves drug delivery efficiency. The proposed theoretical model, dual-frequency transducer design, and experimental validation form an integrated framework that directly links cavitation mechanisms to device optimization and therapeutic efficacy, offering a reliable technical reference for the rational development of ultrasound-mediated TDD systems.
Disrupting neuro-immune crosstalk through cfDNA/NETs degradation by Zr-based nanoenzymes: A therapeutic strategy for airway inflammatory disorders.
Ye Y, Liu M, Zhong H … +11 more , Xu C, Liang K, Lin J, Xie X, Huang Z, Qiu Z, Liu J, Sun X, Li J, Wen W, Tu Z
Biomaterials · 2026 Jun · PMID 42320433 · Publisher ↗
Recent studies have established that neuro-immune interactions are essential for the pathogenesis and persistence of airway inflammation. In line with this, our work demonstrates that neutrophil extracellular traps (NETs...
Recent studies have established that neuro-immune interactions are essential for the pathogenesis and persistence of airway inflammation. In line with this, our work demonstrates that neutrophil extracellular traps (NETs) stimulate neuropeptide secretion-a finding corroborated by elevated neuropeptide levels in nasal polyps from patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and in corresponding murine models. Current nano-scavengers, which primarily rely on electrostatic adsorption to immobilize cell-free DNA (cfDNA)/NETs, face practical limitations, including susceptibility to competing polyanions, limited adsorption capacity, and poor stability. To overcome these drawbacks, we synthesized a class of nanozymes based on high-valent metal ions (Zr or Ce) coordinated with three distinct organic ligands. These nanozymes exhibited robust catalytic degradation of cfDNA/NETs, with Zr-based variants showing the highest efficacy-highlighting the importance of rational metal-ion and ligand selection in designing effective anti-inflammatory nanomedicines. In murine models of ovalbumin (OVA)- or lipopolysaccharide (LPS)-induced airway inflammation, intranasal administration of Zr-based nanozymes significantly reduced cfDNA/NETs levels in inflammatory tissues and decreased total inflammatory-cell counts. Importantly, by degrading cfDNA/NETs, these nanozymes also attenuated neuropeptide release from airway sensory neurons and neuroendocrine cells, thereby suppressing neuro-immune amplification and airway hyperresponsiveness. In summary, our study underscores the importance of a strategically engineered composition for constructing nanozymes capable of efficiently degrading cfDNA/NETs. By simultaneously dismantling the cfDNA/NETs scaffold and disrupting neuropeptide-mediated feed-forward inflammatory loops, these agents offer a dual-mode precision nanomedicine strategy for the treatment of airway inflammatory diseases.
Corrigendum to 'Biomechanical and directional electric field coupling material promotes wound healing through Piezo1-mediated cell migration' [Biomaterials 335 (2026) 124331].
Fan Y, Lin M, Li J … +2 more , Yu Y, Huang Y
Biomaterials · 2026 Jun · PMID 42315396 · Publisher ↗
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Engineering cell ring organoids for efficient establishment of patient-derived orthotopic xenotransplantation (r-PDOX) model in sarcoma.
Xu Y, Tong Z, Li X … +8 more , Yang S, Zhu Q, He Z, Yang H, Liang X, Chen P, Ouyang H, Wu H
Biomaterials · 2026 Jun · PMID 42314236 · Publisher ↗
Patient-derived orthotopic xenotransplantation (PDOX) models have recently emerged as a potential approach for experimental therapeutics and precision medicine in malignant disease. However, the clinical application of P...
Patient-derived orthotopic xenotransplantation (PDOX) models have recently emerged as a potential approach for experimental therapeutics and precision medicine in malignant disease. However, the clinical application of PDOX models was restricted by the varying success rate of the animal models, long generation time, limited number of patient tumor cells and distinct stromal environments. To address this critical barrier, we developed an innovative patient-derived cell ring organoid platform using scaffold-free tumor cell rings. By co-culturing primary sarcoma cells with human skin fibroblasts (HSFs), functional tumor microenvironment (TME) -incorporated organoids were generated within 48 h without exogenous matrices. These organoids enabled rapid establishment of orthotopic xenografts (r-PDOX) in ≤7 days with 100% engraftment efficiency while requiring 50% fewer cells than conventional methods. Crucially, integrated HSFs replicated desmoplastic stroma and vascular networks, preserving patient-specific molecular profiles (transcriptomic correlation r = 0.87) and biological processes. As a preliminary proof-of-concept, the r-PDOX models showed encouraging concordance with patient responses to first-line therapeutics, including ifosfamide and anlotinib, though validation in larger cohorts is required. This platform overcomes key limitations of existing sarcoma models - including cell leakage, phenotypic drift, and protracted timelines, offering a physiologically relevant tool for personalized therapy exploration. The platform represents a promising methodological foundation for rapid sarcoma preclinical modeling in the era of precision oncology.
A biocompatible copper based therapeutic nanoplatform for CD44 specific tumor targeted therapy and potent immune reprogramming.
Fang Y, Tu M, Tu X … +3 more , Zhang H, Li Y, Xu J
Biomaterials · 2026 Jun · PMID 42314235 · Publisher ↗
Despite advances in oncology, the dual challenge of achieving precise tumor-targeted therapy while simultaneously activating antitumor immunity remains a major clinical barrier. In this study, we engineered a biocompatib...
Despite advances in oncology, the dual challenge of achieving precise tumor-targeted therapy while simultaneously activating antitumor immunity remains a major clinical barrier. In this study, we engineered a biocompatible copper-based platform, hyaluronic acid (HA) modified Cu ions based therapeutic (B-Cu/HA), that integrates selective tumor targeting, intrinsic cytotoxicity, and immune activation within a single therapeutic system. Leveraging the HA-CD44 interaction, B-Cu/HA exhibited preferential accumulation and prolonged retention in CD44-overexpressing tumors, while maintaining an excellent biosafety profile. Across multiple cancer models, B-Cu/HA robustly inhibited tumor progression. Mechanistically, it induced cuproptosis through upregulation of FDX1 and aggregation of lipoylated DLAT, and triggered ROS-mediated activation of the cGAS-STING pathway, promoting immunogenic cell death. Transcriptomic analysis revealed activation of hypoxia and cytokine signaling pathways, aligning with enhanced CD8 T-cell cytotoxicity and remodeling of the tumor immune microenvironment. The animal models studies demonstrated that B-Cu/HA significantly suppressed tumor growth without systemic toxicity, and synergistically enhanced the efficacy of the immune checkpoint inhibitors anti-TIGIT. Together, these findings establish B-Cu/HA as a multifunctional, immunomodulatory formulation that offers a clinically translatable strategy to enhance tumor immunotherapy and overcome resistance in CD44-overexpressing tumors.
Stealthy systemic circulation of spatially controlled tumor microenvironment-activated bioadhesive proteinic nanoparticles for pancreatic cancer chemotherapy.
Lee H, Choi HS, Joo KI … +1 more , Cha HJ
Biomaterials · 2026 Jun · PMID 42314234 · Publisher ↗
Pancreatic cancer remains one of the deadliest malignancies, largely due to late diagnosis and the limited efficacy of systemic chemotherapy. Here, we propose a tumor microenvironment-activated bioadhesive nanoparticle p...
Pancreatic cancer remains one of the deadliest malignancies, largely due to late diagnosis and the limited efficacy of systemic chemotherapy. Here, we propose a tumor microenvironment-activated bioadhesive nanoparticle platform designed to enhance intratumoral drug retention and therapeutic efficacy following systemic intravenous administration. The system was based on bioengineered mussel adhesive protein (MAP)-derived nanoparticles that were conjugated with polyethylene glycol (PEG) shielding linked via a matrix metalloproteinase-2 (MMP2)-cleavable peptide, enabling stealth systemic circulation and tumor-specific deshielding. Upon exposure to the MMP2-rich tumor microenvironment, the PEG layer was selectively removed, restoring strong wet tissue adhesion and promoting sustained intratumoral release of anticancer drugs. Gemcitabine-loaded shielded MAP nanoparticles (Gem-S-MNPs) demonstrated efficient drug encapsulation and enzyme-mediated PEG deshielding, which restored MAP adhesiveness and consequently enhanced anticancer efficacy against pancreatic cancer cells compared with free gemcitabine. In vivo evaluation through intravenous systemic administration of Gem-S-MNPs demonstrated superior intratumoral accumulation and prolonged retention of gemcitabine-loaded deshielded MAP nanoparticles (Gem-dS-MNPs), resulting in effective tumor growth suppression without observable systemic toxicity. Histological analyses further confirmed extensive apoptosis and necrosis within tumor tissues following treatment. Collectively, the proposed systemic administrable spatially controlled tumor microenvironment-activated bioadhesive nanoparticle platform offers a promising approach to address key limitations of conventional systemic chemotherapy for pancreatic cancer.
Anisotropic porous hydrogel fiber coating modified titanium modulates the immune microenvironment to enhance endogenous bone regeneration.
Zhao H, Wang J, Xia Z … +5 more , He L, Zhang H, Luo H, Zhao C, Cai K
Biomaterials · 2026 Jun · PMID 42314233 · Publisher ↗
Titanium implants remain limited by their intrinsic bioinertness, which compromises osseointegration and long-term stability. Here, we present an immuno-instructive and structurally anisotropic titanium interface designe...
Titanium implants remain limited by their intrinsic bioinertness, which compromises osseointegration and long-term stability. Here, we present an immuno-instructive and structurally anisotropic titanium interface designed to promote osteogenesis while modulating the osteoimmune microenvironment. A biomimetic hydrogel fibrous coating composed of nano-hydroxyapatites, gelatin methacryloyl, and silk fibroin was engineered via electrospinning and multimodal crosslinking to generate aligned topographical cues. The anisotropic architecture guided bone marrow stromal cells alignment and migration through cytoskeletal remodeling associated with mechanosensitive responses, while concurrently influencing the local immune milieu by suppressing M1 polarization and promoting M2 transition. These results indicate that the coating exhibited immunomodulatory potential by reducing inflammatory and oxidative stress in macrophages, while also directly supporting osteogenic signaling and matrix mineralization in BMSCs. In vivo, the modified implants reduced early fibrotic encapsulation and promoted peri-implant bone formation, supporting a favorable osteoimmune microenvironment for bone integration. These findings suggest that integrating topographical anisotropy with bioactive hydrogel chemistry provides a promising strategy for enhancing the biological performance of titanium implants and promoting osseointegration.
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