Biomaterials[JOURNAL]
Sun
200 papers
A dual-asymmetric hemostatic Janus hydrogel patch inhibits postoperative recurrence and metastasis of triple-negative breast cancer by suppressing COX-2/PGE axis.
Mi D, Liu T, Zou L … +7 more , Wei Y, Zeng J, Nie C, Zeng Y, Wang R, Zhao M, Shi S
Biomaterials · 2026 Nov · PMID 42139922 · Publisher ↗
Surgical resection combined with chemotherapy remains the standard clinical intervention for triple-negative breast cancer (TNBC). However, the elevated expression of COX-2/PGE, often exacerbated by chemotherapeutic agen...
Surgical resection combined with chemotherapy remains the standard clinical intervention for triple-negative breast cancer (TNBC). However, the elevated expression of COX-2/PGE, often exacerbated by chemotherapeutic agents, is significantly associated with high postoperative recurrence and metastasis. Tailored for the TNBC postoperative setting, we developed a photopolymerizable, dual-asymmetric hemostatic Janus hydrogel patch (DJ-Patch) based on the synergistic pharmacodynamic rationale of gambogic acid (GA) and celecoxib (CXB) pairing. The DJ-Patch exhibits a stratified bilayer configuration comprising a rapid-release layer (5% GelMA) encapsulating GA, juxtaposed with an extended-release layer (10% GelMA/2.5% PEGNB) containing the selective COX-2 inhibitor CXB. In vitro study corroborated this differential release modality, revealing asymmetric kinetics wherein GA achieved ∼20% release at 8 h escalating to greater than 60% by day 3, whereas CXB demonstrated ∼10% release at 8 h and ∼30% by day 3. In vivo release profiles further substantiated these findings, demonstrating that CXB exhibited a 2-fold prolonged release duration relative to GA. The asymmetric adhesive design, featuring a high-adhesion interface manifesting adhesion strength 12.5-fold superior to GelMA alone, facilitated rapid intraoperative hemostasis with clotting time reduced to 160 s versus 440 s in untreated controls, and effected efficacious wound sealing as validated in a mouse liver laceration model. In an orthotopic 4T1-Luc TNBC resection model, the DJ-Patch achieved 86% survival, complete tumor clearance by day 7, and suppressed lung metastasis through sustained COX-2/PGE axis inhibition, Treg cell reduction, and remodeled the immunosuppressive tumor microenvironment (TME). Collectively, this integrated platform offers a promising strategy for comprehensive TNBC postsurgical management.
KEAP1-mediated mitochondrial remodeling on stiffness-graded collagen substrates drives hepatocellular carcinoma adaptation.
Elblová P, Calé A, Andělová H … +11 more , Morán L, De Bonis A, Hionides A, Nevzorova YA, Kubovciak J, Jirsa M, Květoň M, Straník J, Lunova M, Cubero FJ, Lunov O
Biomaterials · 2026 Nov · PMID 42139921 · Publisher ↗
Mechanical and structural cues of the extracellular matrix (ECM) regulate tumor cell metabolism and drug response, yet the molecular mediators that link these biophysical signals are unclear. We present an elastically su...
Mechanical and structural cues of the extracellular matrix (ECM) regulate tumor cell metabolism and drug response, yet the molecular mediators that link these biophysical signals are unclear. We present an elastically supported surface platform bioengineered with varying stiffness and collagen fiber anisotropy to replicate the fibrotic and mechanically inhomogeneous liver cancer microenvironment. Using this system, we identify Kelch-like ECH-associated protein 1 (KEAP1) as a mechanoresponsive mediator linking ECM stiffness to mitochondrial dynamics, redox adaptation, and chemoresistance in hepatocellular carcinoma (HCC). In substrate stiffness increase, biphasic KEAP1 expression, time-dependent mitochondrial remodeling via a KEAP1-BCL-2-DRP1 cascade, suppression of reactive oxygen species, and activation of antioxidant and glycolytic transcriptional programs were triggered. RNA sequencing revealed stiffness-dependent repression of mitochondrial fission genes and induction of AGE-RAGE signaling. At a functional level, cells grown in stiffer matrix demonstrated augmented proliferation and chemoresistance to cisplatin and sorafenib with nuclear translocation of NRF2. Multiplex imaging of human HCC tissues confirmed that collagen-rich regions co-localize with high KEAP1 and TOM20 expression, confirming the in vitro findings. This study demonstrates ECM stiffness to be a bioactive material property that guides mitochondrial and redox networks through KEAP1 signaling, and the mechanically tunable collagen platforms to be of a utility for dissection and manipulation of tumor adaptation mechanisms.
Tough and hierarchically-structured silk hydrogel for artificial tendons.
Zhou S, Nie K, Wu B … +9 more , Qin C, Tian J, Li L, Fan Z, Yin Z, Ouyang H, Chen X, Shen W, Huang W
Biomaterials · 2026 Nov · PMID 42139920 · Publisher ↗
Tendon injuries are prevalent in both athletic and general populations, leading to significant pain, lost productivity, and disabilities. However, surgical reconstruction of ruptured tendons remains a clinical challenge...
Tendon injuries are prevalent in both athletic and general populations, leading to significant pain, lost productivity, and disabilities. However, surgical reconstruction of ruptured tendons remains a clinical challenge and requires tough, regenerative artificial tendons to promote functional restoration. Here, inspired by the structure of native tendons, we introduce a facile approach that synergistically combines directional-freezing and hot-stretching strategies to produce tough and hierarchically-structured silk hydrogels, named DFHS hydrogels, for artificial tendons. At a high water content of about 70 wt%, DFHS hydrogels exhibit an ultimate tensile strength of 13.9 MPa, comparable to human anterior cruciate ligament, and a fracture toughness of 45.5 kJ m, 5 times as high as natural rubber. Additionally, the high crystallinity and aligned multi-level structures prolong the degradation and thus improve long-term integrity and mechanical stability both in vitro and in vivo. DFHS hydrogels exhibit multi-level anisotropy, featuring micrometer-scale honeycomb-like pore walls that harbor nanoscale-oriented β-sheets. These bioinspired topological niches induce significant cell alignment, guide the ingrowth of neo-tendon, upregulate pathways related to the extracellular matrix, promote mature tendon formation, and thereby facilitate tendon healing. This strategy, transferable to other semicrystalline polymers, presents a water-based fabrication approach for the development of tough hydrogels toward clinical translations.
Corrigendum to "Adaptive cationic peptide bundles hydrogel for the repair of infected mandibular defects" [Biomaterials 325 (2026) 123613].
Sun Y, Yang X, Liu Y … +6 more , Zhang C, Feng H, Wu D, Ye L, Yu F, Li F
Biomaterials · 2026 May · PMID 42135110 · Publisher ↗
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4-aminopyridine-loaded topical gel for promoting skin regeneration in burn injuries.
Ellur G, Kamaraj M, Rahul VG … +4 more , Yadav D, Elfar JC, V John J, Govindappa PK
Biomaterials · 2026 Nov · PMID 42134250 · Publisher ↗
Burn wounds are a common traumatic injury that impair cellular function and hinder the healing process, often resulting in significant skin loss. While autologous skin grafting is considered the gold standard for treatin...
Burn wounds are a common traumatic injury that impair cellular function and hinder the healing process, often resulting in significant skin loss. While autologous skin grafting is considered the gold standard for treating burns, its widespread use is limited due to donor site morbidity and the requirement for large amounts of tissue. Traditional wound dressings and treatments often fail to ensure complete recovery. Being initially FDA-approved to treat multiple sclerosis, 4-aminopyridine (4-AP) has also been shown to accelerate burn wound closure by modulating keratinocytes and fibroblasts when administered systemically. However, prolonged systemic use of 4-AP can lead to significant side effects. In this study, we aimed to repurpose 4-AP for treating skin burn wounds by delivering it topically using a laponite-gelatin gel formulation. This method allows for non-invasive and localized drug delivery on the burn wound site. We evaluated the physical properties of the 4-AP gel, including shear thinning behavior, drug release kinetics, cytocompatibility, and functional wound closure (48hr) using a scratch assay (>90%). Moreover, our in vivo experiments showed that the 4-AP loaded gel accelerates wound healing by reducing inflammation, thereby enhancing re-epithelialization and angiogenesis, and promoting the transformation of fibroblasts into myofibroblasts. Burn closure in the 4-AP gel group was consistently higher than the control gel from day 6 through day 21, reaching near-complete healing by day 21, whereas control-treated wounds remained partially open. This enhanced closure correlated with accelerated collagen remodeling, as the 4-AP gel significantly increased collagen type I and III deposition and their ratio compared to controls (438% vs. 267%; 288% vs. 215%; ratio 1.7 vs. 1.2; ∗P < 0.05 to ∗∗∗P < 0.0002), indicating improved matrix maturation during burn healing. This novel application of the 4-AP gel could offer a promising alternative to current burn wound therapies, potentially leading to improved outcomes for burn patients.
BFO@Au leveraged membrane necrotherapy: Rapid tumor eradication via membrane oxidation and immune activation.
Wang Z, Zhang F, Zhou B … +8 more , Cui Y, Sun L, Won M, Xu L, Sun J, Wang L, Kim JS, Dong B
Biomaterials · 2026 Nov · PMID 42134249 · Publisher ↗
The rapid development of nanomedicine has significantly improved the targeting and biosafety of cancer therapy. However, most current nanotherapeutics require 4-24 h of intracellular delivery and signaling responses, lea...
The rapid development of nanomedicine has significantly improved the targeting and biosafety of cancer therapy. However, most current nanotherapeutics require 4-24 h of intracellular delivery and signaling responses, leading to delayed responses, increased risks of resistance and metastasis. Achieving efficient tumor cell killing within minutes holds promise for overcoming these limitations and enabling more thorough tumor elimination. In this study, we synthesized a nanosheet material, BiFeO@Au (BFO@Au NSs), which integrates membrane thiol-targeting recognition with potent oxidative-damage capability. By efficiently depleting sulfhydryl groups on the surface of tumor cell membranes and disrupting membrane functional proteins within minutes, BFO@Au NSs rapidly induces membrane dysfunction, triggering metabolic disorders, mitochondrial membrane potential collapse, and redox imbalance, ultimately leading to irreversible necrosis of tumor cells, thereby successfully achieving 'membrane necrotherapy'. This process simultaneously induces an immunogenic cell death (ICD)-like response, effectively promoting the dendritic cell maturation and the M1 polarization of macrophages, enhancing antitumor immune responses and suppressing distant metastasis. Importantly, the oxidative activity of BFO@Au NSs decays rapidly after reacting with tumor membranes, significantly reducing toxicity to biological tissues. This study proposes a new synergistic anti-tumor strategy based on membrane function disruption, providing a theoretical basis and application prospects for efficient and safe nanotherapeutic systems.
Spatiotemporally programmable hydrogel enables NIR-triggered biofilm disruption and mitophagy-driven immunometabolic remodeling for periodontitis.
Zhai J, Yang X, Ren S … +9 more , Wang Y, Chen J, Luo J, Zhu Y, Chen S, Chen S, Lv H, Lin Q, Zhou Y
Biomaterials · 2026 Nov · PMID 42127485 · Publisher ↗
The refractory nature of periodontitis stems from two interrelated factors: the difficulty in eradicating deeply entrenched pathogenic biofilms and the biofilm-induced impairment of mitochondrial autophagy in immune cell...
The refractory nature of periodontitis stems from two interrelated factors: the difficulty in eradicating deeply entrenched pathogenic biofilms and the biofilm-induced impairment of mitochondrial autophagy in immune cells, leading to metabolic dysregulation and persistent inflammation. These processes mutually reinforce each other, creating a self-perpetuating vicious cycle. To address this, we developed a spatiotemporally programmable smart hydrogel (GM hydrogel), constructed on a dynamically crosslinked network of oxidized fucoidan and carboxymethyl chitosan, loaded with silver nanoparticles and EGCG-modified MXene nanosheets (MXene@EGCG-Ag). This near-infrared (NIR) light-responsive platform exhibits excellent injectability, enabling it to completely fill narrow, deep, and irregular periodontal pockets, ensuring intimate contact with pathological sites. The GM hydrogel provides programmed control along both temporal and spatial dimensions. In the temporal dimension, NIR irradiation triggers MXene-mediated mild photothermal effects (<45 °C) that disrupt biofilm structure and facilitate Ag and EGCG penetration into deeper tissues. In subsequent stages, sustained EGCG release restores mitochondrial autophagy, reprogramming immune cell metabolism to improve the immune microenvironment. Spatially, the hydrogel penetrates mature biofilms and delivers comprehensive treatment from the surface through deep gingiva to the alveolar bone interface. Experimental results demonstrate that GM hydrogel disrupts ionic homeostasis and impairs biofilm functionality in Porphyromonas gingivalis, exhibiting potent antibacterial effects. Sustained EGCG release activates the PINK1/Parkin-mediated FOXO pathway, which restores mitochondrial autophagy and induces metabolic reprogramming, thereby suppressing inflammation and promoting alveolar bone regeneration.
Compliant bilayer vascular grafts with in situ heparin functionalization for small diameter vascular regeneration.
Li L, Xu G, Gao N … +5 more , Li L, Li X, Kong M, Yang H, Yin J
Biomaterials · 2026 Nov · PMID 42127484 · Publisher ↗
Given the scarcity of autologous graft donors, a substantial and pressing demand exists for small-diameter (<6 mm) vascular grafts (SDVGs) as viable alternatives in bypass and reconstructive surgeries for the treatment o...
Given the scarcity of autologous graft donors, a substantial and pressing demand exists for small-diameter (<6 mm) vascular grafts (SDVGs) as viable alternatives in bypass and reconstructive surgeries for the treatment of cardiovascular diseases, including coronary artery disease and peripheral artery disease. However, the challenges of compliance mismatch, inadequate endothelialization, and insufficient anticoagulation of SDVGs generally lead to side effects like thrombosis, inflammation and intimal hyperplasia. To address these issues, this study proposes a biomimetic bilayer SDVG with heparin modification fabricated through dry-jet wet spinning. This comprises a reinforced outer layer for sufficient mechanical strength and a flexible inner layer for high compliance, effectively mimicking the mechanical properties of natural vessels. The one-step in-situ heparin coating strategy represents a significant simplification for fabrication, ensuring uniform heparin distribution to prevent platelet aggregation and thrombus formation, and enhancing endothelial cell (EC) adhesion, spreading, and proliferation. The in vivo evaluation of rabbit carotid artery demonstrates that the vascular graft achieves excellent long-term patency without apparent obstruction or thrombosis. Five months post-implantation, compositions similar to native blood vessels are formed, and immunofluorescence staining shows positive expression for ECs and smooth muscle cells and the persistent infiltration of M2-polarized macrophages on the inner surface. The proposed fabrication strategy provides a novel solution for vascular replacement and has potential applications in vascular bypass and reconstruction.
Advances in multi-dimensional targeting probes for precision medicine of breast cancer.
Zhang P, Wu M, Sun L … +5 more , Sun S, Li H, Chen T, Wu A, Li Q
Biomaterials · 2026 Nov · PMID 42119169 · Publisher ↗
Breast cancer (BC) remains the most frequently diagnosed cancer and the second leading cause of cancer-related mortality among women worldwide. Medical imaging is essential in the diagnosis and management of BC, deliveri...
Breast cancer (BC) remains the most frequently diagnosed cancer and the second leading cause of cancer-related mortality among women worldwide. Medical imaging is essential in the diagnosis and management of BC, delivering crucial information about tumor location, heterogeneity, and metastatic progression. Nuclear medicine imaging offers non-invasive functional assessment through probes, which capture biological characteristics of tumors more effectively than conventional structural imaging modalities such as CT or MRI. The identification of specific molecular targets has become pivotal for accurate tumor subtyping, prognosis assessment, and tailoring effective therapies. In this review, these molecular targets are classified according to a three-dimensional spatial framework of BC, encompassing (1) intracellular metabolic processes, (2) cell-surface receptor expression, and (3) the extracellular TME. Through multi-dimensional targeting approaches from intracellular processes to microenvironmental networks, nuclear medicine imaging decodes BC biology: metabolism imaging reveals core cellular functions, receptor imaging identifies actionable therapeutic targets and evaluates molecular expression levels, and TME imaging elucidates complex microenvironmental interactions. Collectively, this spatially-informed targeting strategy allows for the non-invasive evaluation of therapeutic targets, assessment of tumor heterogeneity, and dynamic monitoring of treatment response. Furthermore, these advances are increasingly extending beyond diagnostics toward theranostic applications, where diagnostic probes are paired with therapeutic radionuclides to enable image-guided radioligand therapy. By consolidating current knowledge and outlining future directions, this review aims to inform both clinical practice and the development of next-generation imaging and theranostic platforms in precision oncology.
From clinical exosome analysis to engineered therapy: miR-21-5p-Enriched exosomes reverse thin endometrium via the YAP1 pathway.
Cheng L, Liang B, Chen M … +6 more , Lian R, Mo M, Li M, Chen B, Chen X, Liu J
Biomaterials · 2026 Nov · PMID 42119168 · Publisher ↗
Thin endometrium (TE) is associated with reduced pregnancy rates and adverse obstetric outcomes. While current interventions including hysteroscopic adhesiolysis and hormonal regimens offer partial solutions, functional...
Thin endometrium (TE) is associated with reduced pregnancy rates and adverse obstetric outcomes. While current interventions including hysteroscopic adhesiolysis and hormonal regimens offer partial solutions, functional restoration remains challenging due to the elusive pathogenesis of TE. This work systematically decodes the miRNA landscape of uterine fluid-derived exosomes (UF-Exo) between TE patients and healthy women, uncovering a dramatic downregulation of miR-21-5p (74.0%) and miR-548aa (64.5%) in TE-derived UF-Exo that critically underpins disease progression. Leveraging these insights, a miRNA-reprogramming therapeutics is established based on engineered human umbilical cord mesenchymal stem cell-derived exosome (hUCMSCs-Exo) that precisely orchestrates endometrial cellular proliferation and angiogenic processes. Through sophisticated bioinformatics analysis, YAP1 is identified as a principal downstream target of miR-21-5p. In murine TE models, miR-21-5p-enriched hUCMSCs-Exo successfully reprograms the miR-21-5p/YAP1 signaling axis, driving extraordinary regenerative outcomes: a remarkable 4.4-fold increase in endometrial thickness, significant suppression of fibrosis, and a considerable 33.6-fold enhancement in vascularization. The platform simultaneously elevates endometrial receptivity (233.3% αvβ3 mRNA upregulation) and recalibrates the inflammatory microenvironment. This work identifies novel diagnostic biomarkers and pioneered an innovative therapeutic approach, thereby offering a potential strategy for improving the clinical management of TE.
Harnessing prophylactic vaccines for targeted cancer immunotherapy by phage-guided delivery of cognate antigens to tumors.
Waramit S, Suwan K, Küçük A … +6 more , Benjathummarak S, Cencioni MT, Ashfield R, Gay L, Draper SJ, Hajitou A
Biomaterials · 2026 Nov · PMID 42119167 · Publisher ↗
Immunotherapies hold great promise for cancer treatment, yet only a small fraction of patients respond to current approaches. We introduce a strategy that redirects pre-existing, vaccine-induced immunity to recognize and...
Immunotherapies hold great promise for cancer treatment, yet only a small fraction of patients respond to current approaches. We introduce a strategy that redirects pre-existing, vaccine-induced immunity to recognize and eliminate tumors. This method employs newly engineered phage-derived nanoparticles that achieve multilayered tumor specificity through ligand-mediated cell entry, transcriptional targeting, and the delivery of non-mammalian antigens absent from healthy tissues. By leveraging established immune memory, this platform enables highly specific and potent antitumor responses. We validated this concept using a malaria vaccine prototype for redirecting pathogen-specific immunity toward cancer. Specifically, we exploited the malaria epitope Pb9 (SYIPSAEKI), delivered by phage selectively to tumors in mice previously immunized with the Ad.ME-TRAP vaccine. In vitro, Pb9-expressing tumor cells were selectively recognized and destroyed by immune cells from immunized mice, accompanied by robust interferon-γ and tumor necrosis factor-α production. In vivo, systemic administration of the phage nanocarrier achieved highly selective Pb9 expression in tumors while sparing healthy organs. This tumor-restricted expression induced infiltration of antigen-specific cytotoxic T cells and natural killer cells, activation of pro-inflammatory pathways, and apoptosis within tumors. Interestingly, the combination of Ad.ME-TRAP immunization and phage-mediated Pb9 gene delivery led to complete tumor regression in a substantial proportion of animals, with durable long-term cures in over 40% of treated mice. These findings demonstrate a versatile immunotherapeutic strategy that redirects pre-existing vaccine-induced immune responses toward tumors using phage-derived, tumor-selective vectors. Beyond the malaria model, this platform offers a broadly applicable approach for repurposing preventive vaccines into safe and effective cancer immunotherapies.
A hierarchical self-adjuvanted nanoCRISPR-based vaccine restores endogenous immune recognition and surveillance to amplify adaptive immune responses.
Huang D, Sun D, Ou C … +9 more , Zhang X, Luo R, Kou X, Li X, Li Y, Le H, Li W, You Y, Gong C
Biomaterials · 2026 Nov · PMID 42119166 · Publisher ↗
Tumor vaccines are considered a promising approach in immunotherapy, designed to boost the immune system's capacity to identify tumor-associated antigens and subsequently trigger immune responses against tumors. However,...
Tumor vaccines are considered a promising approach in immunotherapy, designed to boost the immune system's capacity to identify tumor-associated antigens and subsequently trigger immune responses against tumors. However, the inherent genetic instability of tumor cells frequently results in decreased expression or loss of antigen and/or major histocompatibility complex (MHC) expression and upregulation of immune checkpoint molecule PD-L1, thus evading endogenous immune recognition and surveillance. Herein, we developed a hierarchical self-adjuvanted nanoCRISPR-based vaccine (HEDERA) loaded with LSD1/PD-L1 dual-editing CRISPR/Cas9 system, seeking to reinstate the endogenous immune detection and monitoring mechanisms to enhance adaptive immune reactions. Knockdown of LSD1 increases the presence of tumor-specific antigens and major histocompatibility complex class I molecules on the surface of cancer cells, thereby restoring immune recognition. Simultaneously, silencing PD-L1 alleviates the "exhaustion" of T cells and reactivates their cytotoxic activity. Moreover, LSD1 knockdown activates the type I interferon pathway to induce a self-adjuvant effect that enhances innate immune responses and thereby strengthens T cell-mediated adaptive immunity. This dual strategy achieves unprecedented efficacy, with 90% primary tumor inhibition, and demonstrates an 87.3% and 90.6% inhibition rate for post-surgical metastatic and recurrent tumors, respectively. Overall, HEDERA overcomes the single-action constraint of traditional tumor vaccines, and avoids combined medication-related poor patient compliance, delivering a more efficient, convenient integrated tumor immunotherapy solution.
Engineered metallo-albumin nanoscaffolds that target lymph nodes, deliver antigens and activate STING for cancer immunotherapy.
Sun B, Hu F, Dong W … +5 more , Li S, He X, Lovell JF, Ren H, Zhang Y
Biomaterials · 2026 Nov · PMID 42119165 · Publisher ↗
Lymph nodes serve as strategic targets for cancer vaccines by enhancing interactions with antigen-presenting cells (APCs) and promoting immune activation. Herein, we report that serum albumin can be chemically modified v...
Lymph nodes serve as strategic targets for cancer vaccines by enhancing interactions with antigen-presenting cells (APCs) and promoting immune activation. Herein, we report that serum albumin can be chemically modified via in situ reduction with a short PEG linker, which subsequently coordinates with Mn to generate a lymph nodes targeting metallo-albumin nano-scaffold (MANS) capable of chelating His-tagged antigens and immunostimulatory adjuvants. Maintaining the "hitchhiking" effect of albumin, the MANS chelating antigens (E7 or AH1) accumulates in lymph nodes, where it triggers the responsive release of metal ions and adjuvants to synergistically activate the cGAS-STING pathway. Following uptake by bone marrow dendritic cells (BMDCs), MANS promoted the expression of maturation markers and cytokine release. In multiple murine TC-1 and CT26 tumor models, the MANS vaccine suppresses tumor growth and prolongs survival while elevating antigen-specific CD8 T cells frequency by an order of magnitude; however, these effects were not observed in STING-knockout mice (STING-KO). The MANS vaccine also remodeled the tumor immune microenvironment (TME) by downregulating immunosuppressive cells in the tumor tissues with long-term immune memory, verified by a tumor rechallenge model.
A dual-channel electron expressway triggers piezocatalytic ferroptosis-mitochondrial catastrophe cascade for anti-glioblastoma therapy.
Zou Y, Mo Y, Yang J … +8 more , Wu J, He B, He S, Bao Y, Miao Z, Lin H, Wang G, Zhao X
Biomaterials · 2026 Nov · PMID 42114378 · Publisher ↗
Glioblastoma (GBM) remains clinically challenging due to its pronounced resistance to conventional chemotherapy. Ferroptosis, an iron-dependent form of programmed cell death, has emerged as a promising alternative, yet i...
Glioblastoma (GBM) remains clinically challenging due to its pronounced resistance to conventional chemotherapy. Ferroptosis, an iron-dependent form of programmed cell death, has emerged as a promising alternative, yet its efficacy is limited by the hypoxic tumor microenvironment and adaptive mitochondrial defenses. To overcome these limitations, we developed a piezoelectric nanoplatform (V-BT@PDA@PMS) comprising double-vacancy-engineered barium titanate (BaTiO) nanoparticles, coated with polydopamine (PDA), and loaded with peroxymonosulfate (PMS). This platform constructs a "Dual-Channel Electron Expressway" to significantly amplify ultrasound (US)-triggered generation of sulfate radicals (⋅SO). Internally, barium and oxygen vacancies within the BaTiO lattice facilitate charge carrier separation; externally, the tumor-acid-responsive PDA coating optimizes PMS adsorption and activation via imino protonation. The resulting massive ⋅SO yield exerts a dual-pronged effect: it directly initiates lipid peroxidation to drive ferroptosis and precipitates intracellular Ca as CaSO. This localized Ca depletion triggers profound mitochondrial Ca efflux and the irreversible opening of the mitochondrial permeability transition pore (mPTP). The subsequent structural collapse facilitates a secondary iron influx, establishing a self-amplifying cycle of reactive oxygen species (ROS) generation via Fenton-like reactions. By systematically dismantling mitochondrial defenses against ferroptosis, this cascade achieves a 2.9-fold enhancement in temozolomide (TMZ) chemosensitivity in vitro and demonstrates significant tumor inhibition in chemoresistant in vivo models. Overall, this study elucidates a physical-biochemical mechanism for electron-transport-mediated mitochondrial destabilization, offering a rational design strategy for piezocatalytic nanotherapeutics against drug-resistant malignancies.
Injectable amyloid-structured hydrogel incorporating amorphous calcium phosphate promotes periodontal tissue regeneration by mimicking enamel matrix proteins (EMPs).
Yu K, Li Y, Li X … +8 more , Chen Z, Li F, Zhang S, Zhou X, Zhang K, Lu M, Yang P, Zhang X
Biomaterials · 2026 Nov · PMID 42114377 · Publisher ↗
Periodontitis is the leading cause of tooth loss in adults. Inspired by the role of enamel matrix proteins (EMPs) in promoting periodontal regeneration in vivo and the β-sheet-rich structure of their main component, amel...
Periodontitis is the leading cause of tooth loss in adults. Inspired by the role of enamel matrix proteins (EMPs) in promoting periodontal regeneration in vivo and the β-sheet-rich structure of their main component, amelogenin (Am), we developed an amyloid fibril-based hydrogel composed of bovine serum albumin (BSA), reduced glutathione (GSH), and amorphous calcium phosphate (ACP). Within this system, the self-assembled amyloid fibril network of BSA serves as a biomimetic scaffold. GSH plays a dual role by acting as a mild reducing agent that induces protein phase transition and gelation, while also stabilizing ACP through Ca coordination. We propose that this multifunctional system partially recapitulates key structural and ionic features associated with EMP-mediated periodontal regeneration, thereby promoting periodontal repair without the need for exogenous growth factors.
A host-guest supramolecular delivery system for heat-inducible RNA editing of survivin for liver cancer therapy.
Huang Y, Li B, Shen Z … +4 more , Xie X, Han W, Xu X, Ping Y
Biomaterials · 2026 Nov · PMID 42114376 · Publisher ↗
Precise and controllable RNA editing presents a powerful therapeutic strategy for oncogene silencing in cancer treatment. Here, we introduce a photothermal-activatable host-guest supramolecular delivery system enabling s...
Precise and controllable RNA editing presents a powerful therapeutic strategy for oncogene silencing in cancer treatment. Here, we introduce a photothermal-activatable host-guest supramolecular delivery system enabling spatiotemporally regulated expression of CasRx, a compact RNA-guided RNA endonuclease, for targeted survivin mRNA knockdown in hepatocellular carcinoma. The modular platform is constructed through dynamic assembly of β-cyclodextrin-conjugated polydisulfide and adamantane-functionalized conjugated small molecules through host-guest interactions, enabling the integration of photothermal agents into the delivery vectors that can encapsulate the heat-inducible expression of plasmid encoding CasRx. Upon the near-infrared (NIR) laser irradiation, the moieties containing conjugated small molecules can convert light to heat so as to trigger the specific expression of CasRx in tumor tissue, leading to efficient and selective degradation of survivin transcripts. This supramolecular platform integrates the photothermal switch and delivery carriers and precisely controls RNA editing in vivo, avoiding potential systemic toxicity induced by off-target delivery. Our study establishes a programmable and precise RNA regulation platform in vivo by means of supramolecular assembly for safe, tunable, and effective RNA-based cancer therapy.
Piezo-metastructured arrays enhance osteoblast mitochondrial quality control to promote osseointegration under osteoporotic conditions.
Peng S, Wang K, Ning X … +7 more , Li B, Zhang M, Hu D, Lei Y, Wang Y, Zhou J, Han Y
Biomaterials · 2026 Nov · PMID 42114375 · Publisher ↗
Titanium (Ti)-based implants often exhibit poor osseointegration in osteoporotic bone defects, primarily due to osteoporosis frequently accompanied by excessive reactive oxygen species (ROS), which induce mitochondrial o...
Titanium (Ti)-based implants often exhibit poor osseointegration in osteoporotic bone defects, primarily due to osteoporosis frequently accompanied by excessive reactive oxygen species (ROS), which induce mitochondrial oxidative stress within osteoblasts, leading to dysfunctional mitochondria. To address this challenge, a piezo-metastructured array composed of BaTiO nanorods decorated with hydroxyapatite (HA) nanoparticles (termed as BTH array) was constructed on Ti, which can significantly enhance piezoelectric potential (PP) under low-intensity pulsed ultrasound (LIPUS) treatment. Based on the simulation results, the enhanced PP of BTH array under LIPUS arises from the effects of nanorod pattern induced acoustic impedance matching and the overlapping built-in electric field at BaTiO/HA interface. The elevated PP activates voltage-gated calcium channels in osteoblasts under osteoporosis mimicking conditions, allowing Ca released from degraded HA to flux into cells and appropriately elevate mitochondrial calcium levels, thereby promoting ATP synthesis. The enhanced ATP synthesis supports cytoskeletal remodeling of cells, thereby triggering migrasome formation to eliminate damaged mitochondria and promote the fission of healthy ones. This process restores mitochondrial quality control, leading to the mitigation of mitochondrial oxidative stress and ultimately enhancing osseointegration of Ti-based implants in osteoporosis bone. Thus, piezo-metastructured array coating mediated ATP synthesis in osteoblasts under LIPUS represents a promising strategy to improve implant osseointegration under osteoporosis conditions.
Bioelectric ink bridge: An electroactive casein bioink for cartilage regeneration by actively restoring the electrophysiological niche.
Zhu S, Zhou Z, Chen X … +11 more , He X, Yang L, Lei J, Pei J, Zhao W, Yang Y, Yi M, Zhu W, Zhao Z, Pan H, Liu H
Biomaterials · 2026 Nov · PMID 42114266 · Publisher ↗
The development of bioinks that recapitulate key physiological cues remains a central challenge in 3D bioprinting. Although endogenous bioelectric signals are crucial regulators of cell migration, proliferation, and matr...
The development of bioinks that recapitulate key physiological cues remains a central challenge in 3D bioprinting. Although endogenous bioelectric signals are crucial regulators of cell migration, proliferation, and matrix assembly, they are rarely incorporated into bioink design. Here we present a filler-free electroactive bioink, quaternized-methacrylated casein (QCMA), that integrates intrinsic ionic conductivity with high-resolution digital light processing (DLP) bioprinting. Quaternization markedly improves casein solubility and optical clarity (>90% solubility) while introducing permanent cationic moieties that, together with mobile counterions, enhance charge transport in hydrated constructs; subsequent methacrylation enables rapid photocrosslinking and high-fidelity DLP printing (>95% dimensional accuracy in X-Y and Z). With an optimized cationic density, QCMA maintains chondrocyte viability, promotes cell adhesion and recruitment, and provides broad-spectrum antibacterial activity. Under a physiologically relevant pulsed electric field (150 mV/mm), QCMA-laden constructs activate MAPK-associated signaling, enhance chondrocyte migration and proliferation, and upregulate key chondrogenic markers (ACAN, SOX9, COL2A1, and TGF-β1), leading to increased cartilage matrix deposition. In a rat osteochondral defect model, QCMA implantation reduces local impedance and improves voltage recovery within the defect region, accompanied by increased Cx43 expression, suggesting enhanced gap-junctional communication and improved cartilage repair. Collectively, QCMA establishes a bioelectric niche-oriented strategy for next-generation regenerative bioinks by coupling filler-free electroactivity with DLP printability and therapeutic functionality.
Extracellular matrix properties, interstitial flow, and VEGF gradients shape trophoblast behavior in a pumpless Trophoblast Invasion-on-Chip (TIoC).
Delon LC, Busek M, Lal DL … +8 more , Heesakkers RC, Wergeland TJ, Stokowiec J, Socha AJ, Combriat TM, Golovin A, Boichuk Y, Krauss S
Biomaterials · 2026 Nov · PMID 42107135 · Publisher ↗
Placental trophoblast invasion into the maternal endometrium is a critical step in establishing the maternal-fetal interface during implantation. In vitro, this complex process can be partially modeled using a Trophoblas...
Placental trophoblast invasion into the maternal endometrium is a critical step in establishing the maternal-fetal interface during implantation. In vitro, this complex process can be partially modeled using a Trophoblast Invasion-on-Chip (TIoC) platform. In this study, we used an in-house-developed, pumpless, recirculating "loop-in-loop" microfluidic device that generates interstitial flow (IF) within a tissue compartment to optimize indirect co-culture of cytotrophoblast BeWo cells with human umbilical vein endothelial cells (HUVECs). Eight extracellular matrix (ECM) conditions were tested, including fibrin-based matrices and laminin/collagen-based composites. Pure fibrin ECMs were less porous and stiffer than laminin/collagen matrices; however, mixed ECMs exhibited increased softness and porosity due to structural heterogeneity. BeWo cells demonstrated enhanced migration in fibrin-based mixtures and upregulated markers associated with the extravillous trophoblast phenotype. In contrast, HUVECs did not exhibit migration under any ECM condition. Differences in trophoblast migration were associated with ECM physical properties, biochemical composition, and degradability, and vascular endothelial growth factor (VEGF) diffusion within the matrices. Additionally, the microfluidic device generated unidirectional interstitial flow and established a negative VEGF gradient, which may in part arise from BeWo cell secretion, together with ECM porosity, influenced BeWo cell migration and differentiation in an ECM-dependent manner. Complementary experiments using primary cytotrophoblasts (CTBs) revealed a more restricted, ECM-dependent migration pattern, with a preference for Fibrin over more complex matrices such as Fibrin-Geltrex. Overall, this study demonstrates a clear relationship between trophoblast behavior the, physical and biochemical ECM properties, and the microfluidic flow dynamics. These findings highlights the importance of tuning biochemical, mechanical, and fluidic cues to better elucidate the biomechanical drivers of trophoblast invasion.
Microvascular remodeling strategy for skin rejuvenation through microenvironmental reprogramming and appendage restoration.
Zhou J, Jiang S, Wang L … +6 more , Dong T, Yu L, Li H, Gao Z, Wu J, Lin K
Biomaterials · 2026 Nov · PMID 42107134 · Publisher ↗
Skin photoaging, induced by excessive ultraviolet exposure, leads to microvascular and appendage degeneration, extracellular matrix degradation, and cellular senescence. The limited efficacy of current treatments for pho...
Skin photoaging, induced by excessive ultraviolet exposure, leads to microvascular and appendage degeneration, extracellular matrix degradation, and cellular senescence. The limited efficacy of current treatments for photoaging is partly due to underlying microvascular dysfunction. This study introduces a microneedle patch incorporating decellularized adipose-derived matrix (DAM) to enhance microvascular remodeling and mitigate photoaging. In vitro studies demonstrate that DAM enhances the function of photoaged endothelial cells via the VEGFA/PI3K/Akt pathway while simultaneously alleviating senescence in both fibroblasts and keratinocytes through intercellular communication. In a UVB-induced photoaged mouse model, DAM promotes angiogenesis, reduces matrix metalloproteinase expression, and stimulates collagen synthesis, ultimately restoring local homeostasis and reversing aging signs. Notably, DAM treatment not only reverses these signs but also regulates the hair follicle cycle, underscoring its dual impact on appendage regeneration and microvascular repair. In conclusion, the integration of DAM into a microneedle patch provides a clinically translatable and minimally invasive platform for addressing photoaging. These findings not only advance the understanding of photoaging mechanisms but also propose a novel microvascular-focused strategy for skin regeneration. Future research will focus on optimizing patch design and establishing standardized DAM quality control protocols, with potential applications in other age-related disorders.
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