Acta biomaterialia最新文献

{"title":"Nanomechanics of mandible wear in insects.","authors":"Dilanka I Deegala, Jonathan G Pattrick, David Labonte","doi":"10.1016/j.actbio.2026.10.011","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.10.011","url":null,"abstract":"<p><p>Many animals rely on specialised mouthparts to process food. Because this is a mechanically demanding task, mouthparts often wear, with potentially serious consequences for feeding performance and thus fitness. The biomechanics of wear are therefore of clear biological relevance, but remain poorly understood, especially in insects, where conventional engineering wear tests are hard to implement. Here, we present a nanomechanical characterisation of the mandibular epicuticle of three insect species: two leaf-cutting specialists, one with and one without transition-metal inclusions, and an omnivore. Contrary to predictions from simple engineering wear theory, wear resistance was neither directly proportional to indentation hardness nor inversely proportional to wear load. We suggest that this discrepancy arises in part from the high hardness-to-modulus ratio of mandibular epicuticle, which renders indentation hardness a poor proxy for resistance to plastic deformation. A simple elasto-plastic wear model qualitatively captures the main discrepancies between experiment and theory, and points to a revised set of wear proxies that may allow at least a qualitative ranking of biological materials via iso-performance lines on Ashby plots. Yet, as with most wear models, the wear coefficient remains unpredictable, a limitation strikingly illustrated by the increase in epicuticular wear resistance upon hydration despite a decrease in both hardness and modulus. Together, these observations suggest that purely plastic wear models may often be inadequate for biological materials with a high hardness-to-modulus ratio, and that even elasto-plastic models require careful validation against experimental wear assays. Significance statement Wear limits the functional lifespan of biological tools; however, quantifying, let alone predicting, wear in small, heterogeneous materials is often challenging. In this study, we directly measure nanoscale wear in insect mandibular cuticle and compare our findings with predictions derived from common mechanical wear models. Because of its high hardness-to- modulus ratio, insect epicuticle-like many biomaterials-exhibits an elasto-plastic mechanical response, which can be captured by extending existing approaches with a lumped-parameter elasto-plastic model. The agreement between the model and experiment reveals why using standard proxies can yield even qualitatively incorrect wear rankings and suggests updated elasto-plastic metrics for comparing wear resistance across cuticles and other polymeric biomaterials.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent brain mechanics are linked to microstructural changes.","authors":"Mayra Hoppstädter, Kevin Linka, Marion Schmicke, Ellen Kuhl, Markus Böl","doi":"10.1016/j.actbio.2026.10.010","DOIUrl":"10.1016/j.actbio.2026.10.010","url":null,"abstract":"<p><p>Accurate knowledge of brain tissue mechanics is essential for understanding the pathologies that cause mechanical changes and for developing reliable computer models for neurosurgical procedures. However, the age-related changes in brain mechanics and their microstructural basis are not fully understood. In this study, we examined age-related changes in brain mechanics and microstructure in porcine tissue across five age groups, from early development to young adulthood. Mechanical tests in tension and compression were performed in different anatomical regions, including an anisotropic characterization of the corpus callosum. We used Bayesian parameter identification to estimate material parameters based on isotropic, hyperelastic Ogden and anisotropic, hyperelastic Gasser-Ogden-Holzapfel models under the assumption of large deformations with finite strains. Histological analyses additionally quantified myelin, cell, glia, and neuron measures. Our results revealed nonlinear age dependencies of tensile and compressive mechanics accompanied by clear age-dependent microstructural differences. Notably, myelin- and glia-related measures were the most consistent positive correlates of stiffness. Further, mediation analysis suggested that microstructure, particularly glia-related features, may serve as a measurable intermediate link between age and mechanics. These findings provide a microstructurally informed basis for more realistic, age-dependent computational brain models. Statement of Significance: In order to develop realistic computational models of the brain, it is essential to understand why brain mechanics change with age. While previous work has described age-dependent mechanical behavior, the structural basis of these changes remains unclear. In this study, we combine previously published mechanical data with new, sample-specific histological measurements across development. The key innovation is the use of mediation analysis to test for a measurable statistical link between microstructural changes and mechanics while accounting for the direct effect of age. This approach provides more mechanistic insight than age-dependent mechanical characterization or simple correlation alone. It also helps identify which tissue components are most relevant for explaining developmental changes in brain mechanics.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Gastric ulcers: Biomaterial-based strategies for tissue regeneration and future perspectives on environment-designed biomaterials\" [Acta Biomaterialia 222 (2026) 95-109].","authors":"Caio F C Souza, Inês Vilela de Sousa, Henrique Fernandes-Mendes, Ricardo Marcos-Pinto, Alvaro Mata, Helena S Azevedo, Pedro L Granja","doi":"10.1016/j.actbio.2026.09.050","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.09.050","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin-loaded multi-enzymatic metal-organic framework nanozyme mediates metabolic reprogramming via multiple energy blockades to boost tumor immunotherapy.","authors":"Longyue He, Tiemin Li, Liye Wang, Wei Wang, Linna Chang, Zhou Shen, Lining Zhao, Xiaoping Yin, Leyong Zeng","doi":"10.1016/j.actbio.2026.10.014","DOIUrl":"10.1016/j.actbio.2026.10.014","url":null,"abstract":"<p><p>Glycolytic metabolism of tumor cells suppresses the activity of immune cells, and multiple blocking energy supply and remodeling the metabolic microenvironment are important strategies to enhance immunotherapy. Using manganese-doped porphyrin metal-organic framework (MOF) as a carrier, by depositing ultrasmall Au nanoparticle (AuNPs), loading metformin (MET) and coating polydopamine (PDA), an integrated MOF@Au/MET@PDA nanozyme with multi-enzyme activity was constructed for enhancing antitumor immunotherapy. MOF@Au/MET@PDA nanozyme possessed glutathione peroxidase/glucose oxidase/peroxidase/catalase-like activity, by which the reactive oxygen species generation was greatly enhanced, and the mitochondrial function was damaged. Moreover, by consuming glucose and inhibiting the synthesis of adenosine triphosphate, the MOF@Au/MET@PDA nanozyme effectively blocked the energy supply and hindered glycolysis. Furthermore, the MOF@Au/MET@PDA nanozyme up-regulated the Caspase 3/7 level and down-regulated the expression of programmed death ligand-1, by which the apoptosis was induced and the immunogenic cell death was triggered. Under the combined immunotherapy, the immune response was activated, and the primary and metastatic tumors were greatly inhibited, proving the strong immune effect of MOF@Au/MET@PDA nanozyme. STATEMENT OF SIGNIFICANCE: Tumor metabolic plasticity undermines the efficacy of single-pathway immunotherapy. In this work, a multi-enzymatic MOF@Au/MET@PDA nanozyme is engineered to mediate metabolic reprogramming by blocking energy supply through glucose depletion and suppression of glycolysis/oxidative phosphorylation. It amplifies oxidative stress, triggers ICD, down-regulates PD-L1, and remodels the immunosuppressive microenvironment. This nanozyme effectively inhibits primary breast tumors and lung metastasis, providing a metabolic-reprogramming strategy to boost tumor immunotherapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid-degradable hollow calcium-manganese nanocarriers integrate calcium stress, redox catalysis, and antitumor immunity for lung cancer therapy.","authors":"Wei Liu, Maopeng Yang, Fengjiao Wang, Hongtao Yin, Shuyi Zhai, Fucheng Zhou, Qiang Gao, Jinrui He, Yanbin Zhao, Jinfeng Ning","doi":"10.1016/j.actbio.2026.10.015","DOIUrl":"10.1016/j.actbio.2026.10.015","url":null,"abstract":"<p><p>Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality, while acquired resistance to EGFR-targeted therapy and an immunosuppressive tumor microenvironment continue to limit therapeutic efficacy. Here, we developed a tumor cell membrane-coated, acid-degradable hollow calcium-manganese nanoplatform loaded with gefitinib (CM@HCC-Mn/Gef) for combined redox modulation and antitumor immune activation. Under acidic and redox-active conditions, CM@HCC-Mn/Gef released gefitinib, Ca²⁺, and Mn²⁺, leading to intracellular Ca²⁺ accumulation, mitochondrial depolarization, ATP depletion, reactive oxygen species generation, glutathione consumption, GPX4 downregulation, and lipid peroxidation. These coordinated effects induced ferroptosis-associated oxidative damage and immunogenic cell death (ICD), characterized by cell-surface calreticulin exposure and HMGB1 redistribution, and subsequently promoted dendritic cell maturation and T-cell activation. In gefitinib-resistant NSCLC cells, CM@HCC-Mn/Gef produced substantially greater cytotoxicity than free gefitinib, indicating that multimechanistic stress amplification enhanced the therapeutic response of resistant tumor cells. In immunocompetent syngeneic LLC tumor models, the nanoplatform inhibited primary tumor growth, increased tumor-infiltrating T cells, alleviated immunosuppressive features of the tumor microenvironment, and delayed contralateral secondary tumor progression. Combination with anti-PD-1 further enhanced tumor suppression and systemic immune activation. Collectively, CM@HCC-Mn/Gef integrates targeted drug delivery, calcium-associated mitochondrial stress, redox disruption, ferroptosis-associated damage, and immune activation, providing a biomimetic nanotherapeutic strategy for NSCLC chemoimmunotherapy. STATEMENT OF SIGNIFICANCE: Conventional nanocarriers often provide drug delivery without coordinating multiple tumor-specific stresses and immune activation. This study introduces a tumor cell membrane-coated, acid-degradable hollow calcium-manganese nanoplatform that co-releases gefitinib, Ca²⁺, and Mn²⁺ in the tumor microenvironment. The material couples calcium-associated mitochondrial dysfunction with manganese-driven redox catalysis, thereby enhancing oxidative damage, lipid peroxidation, and immunogenic cell death-associated responses. It also improves tumor accumulation, promotes dendritic cell maturation and T-cell activation, and enhances anti-PD-1 therapy in immunocompetent lung cancer models. This work establishes a direct link between biomaterial composition, stimulus-responsive degradation, catalytic function, and antitumor immunity, offering a versatile design strategy for biomaterials-enabled chemoimmunotherapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial induction of mitochondrial calcification as a trigger for cancer immunotherapy.","authors":"Kaixin Zhang, Hanhui Li, Zhuoxin Wang, Hongkun Wu, Li Shi, Qingqing Feng, Hongye Guan, Ben Wang","doi":"10.1016/j.actbio.2026.10.016","DOIUrl":"10.1016/j.actbio.2026.10.016","url":null,"abstract":"<p><p>Tumor calcification shows promise as a clinical predictor of tumor response and often involves mitochondrial calcification, which provides mineral precursors for extracellular deposition. However, the methods available for regulating mitochondrial calcification in tumor calcification therapy are limited. Herein, we designed and synthesized (4-carboxybutyl) triphenylphosphonium bromide (CTPP)-functionalized calcium peroxide (CaO₂) nanoparticles (CTPP/CaO₂) to achieve selective induction of mitochondrial calcification in hepatocellular carcinoma cells. The CTPP/CaO₂-induced mitochondrial calcification sustains elevated intracellular calcium ion (Ca²⁺) and reactive oxygen species (ROS), exacerbates mitochondrial dysfunction, and triggers tumor cell death via pyroptosis. Pyroptosis further promotes the release of intracellular contents and exposure of calreticulin on the cell membrane, effectively activating the antitumor immune response in vivo. This mitochondrial calcification strategy integrates direct killing of tumor cells with subsequent activation of the antitumor immune response, thus providing a promising approach for engineering mitochondrial calcification with potential applications in cancer therapy. STATEMENT OF SIGNIFICANCE: Tumor calcification is a promising anticancer therapeutic strategy, but most existing methodologies are confined to non-specific extracellular mineralization with unsatisfactory targeting precision. We herein report a mitochondria-targeted nanoplatform that selectively initiates mitochondrial calcification against hepatocellular carcinoma. The resultant mitochondrial impairment and persistent ROS overproduction drive tumor pyroptosis, enabling direct tumor ablation and robust antitumor immune activation. Meanwhile, in situ tumor calcification augments CT/MR imaging contrast. This mitochondria-targeted calcification strategy achieves integrated theranostics and provides a potential strategy for refractory solid malignancies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiscale Meniscus Mechanics under Unconfined Compression: Composite Fibril-Reinforced Biphasic Modeling across Infinitesimal to Physiological Cumulative Strain Regimes.","authors":"Sayed Shahabodin Hashemi, Manijhe Mokhtari-Dizaji, Jose Luis Martin-Rodriguez","doi":"10.1016/j.actbio.2026.10.012","DOIUrl":"https://doi.org/10.1016/j.actbio.2026.10.012","url":null,"abstract":"&lt;p&gt;&lt;p&gt;To investigate the mechanical roles of proteoglycan aggregates, interstitial fluid, and the collagen fibrillar network in meniscal mechanics, we developed and experimentally validated a composite fibril-reinforced biphasic (CFRB) model based on a heterogeneous and anisotropic structural description of the meniscus and tested whether shear wave elastography (SWE) could independently reflect matrix‑dominated and fibril‑engaged behavior. Focusing on the pars intermedia, 21+12+(6 × 5) disc specimens underwent unconfined compression across cumulative strains extending into the nonlinear regime to identify model parameters and evaluate strain-rate effects, pressurization, and interstitial fluid transport. Within classical fibril-reinforced poroelastic (FRB) theory, the equally distributed collagen fibrillar network across three orthogonal directions corresponded to linear progressive fibrillar recruitment, while dynamic stiffness amplitude exhibited heterogeneous yet systematically evolving behavior consistent with interstitial fluid transport and pressurization. With nonlinear fibrillar reinforcement, the FRB model showed substantial errors in fibril modulus, whereas the CFRB framework, incorporating frequency-time circular poroelastic analysis, identified lateral strain, biphasic parameters, and mechanical-regime thresholds, and captured the experimental curves and strain heterogeneity. These findings were supported by inverse analysis, finite element methods, meniscal tensile mechanics, and SWE measurements in the plane perpendicular to loading. Increasing strain rate increased the elastic fraction and enabled derivation of pressurization convergence equations, whereas the equilibrium modulus showed no significant rate dependence, consistent with matrix-deformation estimates from the normalized threshold curve and corresponding SWE measurements; this range is proposed as a mechanical regime suitable for evaluation of matrix-related degeneration and elastographic assessment. This framework stratifies cumulative strain, decodes elastography into matrix versus fibril responses, and advances meniscal constitutive modeling toward clinical translation. STATEMENT OF SIGNIFICANCE: Quantifying solid-phase moduli, lateral strain evolution, nonlinear fibril-recruitment thresholds, and permeability parameters can provide insights into the mechanics of porous menisci. Here, Hashemi S.S. et al. introduce a composite fibril-reinforced biphasic (CFRB) framework with poroelastic transformation equations that quantitatively resolves matrix- and fibril-dominated mechanical regimes across cumulative compressive strains from infinitesimal to physiological levels. The framework quantitatively resolved matrix and fibrillar contributions within the matrix-dominated regime, revealing that fibrillar reinforcement also modulated the matrix-deformation response, potentially contributing to anisotropic behavior. The low-strain regime provides a mechanically meaningful ran","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective treatment of orthotopic liver cancer with bifunctional embolization microspheres.","authors":"Baoqu Zhang, Jianke Li, Jianmin Zhao, Yanwu Peng, Perumal Ramesh Kannan, Han Zhang, Xiangdong Kong, Rui Tang, Ruibo Zhao","doi":"10.1016/j.actbio.2026.10.017","DOIUrl":"10.1016/j.actbio.2026.10.017","url":null,"abstract":"<p><p>Transcatheter arterial chemoembolization (TACE) is a minimally invasive procedure used widely for the treatment of unresectable hepatocellular carcinoma (HCC). However, embolization-induced hypoxia upregulates VEGF, and the resulting angiogenic response contributes to tumor recurrence, further limiting the efficacy of TACE against HCC. Herein, we present a multifunctional embolic microsphere system in which sorafenib (SRF) and calcium carbonate (CaCO₃) nanoparticles are rationally encapsulated within sodium hyaluronate microspheres (SRF-CaCO₃@SH MSs) via microfluidic technology. The microspheres exhibited a bowl-shaped morphology with tunable diameters, which enhances in vivo embolic stability through mechanical interlocking between adjacent microspheres. In an acidic tumor microenvironment (TME), pH-triggered release of Ca²⁺ (23.9%) and SRF (65.7%) far exceeded neutral conditions. SRF-CaCO₃@SH MSs maintained >85% HUVEC viability and reduced VX2 cell viability to 24.3%, showing maximal cytotoxicity under acidic conditions. After intra-arterial injection, the microspheres occluded tumor-feeding arteries; Ca²⁺ released in the acidic TME inhibited angiogenesis, and CaCO₃ neutralized TME acidity, counteracting immunosuppression. In a rabbit VX2 orthotopic HCC model, DSA-guided TACE achieved effective occlusion, slowest tumor growth, largest necrosis, and marked downregulation of CD31, Ki67, and VEGF, without systemic toxicity. Combining morphological design, pH-responsive occlusion, TME neutralization, and anti-angiogenesis, this embolic system synergistically enhances TACE and shows strong clinical potential. STATEMENT OF SIGNIFICANCE: Conventional liver cancer embolization frequently fails due to hypoxia-driven angiogenesis and subsequent tumor recurrence. We developed a dual-functional embolic microsphere (SRF-CaCO₃@SH MS) that integrates stable vascular occlusion with active modulation of the tumor microenvironment. Utilizing microfluidics, we fabricated bowl-shaped sodium hyaluronate microspheres that mechanically interlock to ensure durable embolization. Under acidic tumor conditions, calcium carbonate neutralizes pH and releases Ca²⁺, which synergizes with sorafenib to inhibit angiogenesis and induce apoptosis. In a rabbit orthotopic HCC model, this system demonstrated superior tumor control and necrosis without inducing systemic toxicity. This work presents a microenvironment-responsive embolization strategy integrating durable vascular occlusion, pH modulation, and anti-angiogenic therapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A 3D lymphatics-on-a-chip reveals matrix stiffness dependent VEGFR-2 and VEGFR-3 contributions to lymphangiogenesis.","authors":"Lauren C Richardson, Issahy Cano, Anna M Kolarzyk, Esak Lee","doi":"10.1016/j.actbio.2026.10.013","DOIUrl":"10.1016/j.actbio.2026.10.013","url":null,"abstract":"<p><p>The lymphatic system regulates fluid homeostasis and host immunity by draining interstitial fluid and immune cells and transporting them to the lymph nodes. Lymphatic capillaries, essential for capturing interstitial material, undergo lymphangiogenesis to form new lymphatic vessels from existing ones. However, the roles of the vascular endothelial growth factor (VEGF) family and their receptors in lymphangiogenesis under varying matrix stiffness conditions remain unclear. We examine lymphangiogenesis in response to VEGF-A, VEGF-C, and VEGF-C156S across different matrix stiffnesses and evaluate the effects of VEGFR-3 and VEGFR-2 inhibition in a three-dimensional (3D) lymphatics-on-a-chip model. In the model, VEGF-C induced the greatest lymphangiogenesis across all tissue stiffnesses. VEGF-A driven lymphangiogenesis was also notable in compliant and stiff matrices. VEGF-C156S-induced lymphangiogenesis was weaker than that in VEGF-A and VEGF-C conditions. Given that VEGF-C promoted the greatest sprouting across all matrix conditions and could interact with both VEGFR-3 and VEGFR-2, we examined VEGF-C driven lymphangiogenesis under VEGFR-3 and VEGFR-2 inhibition. In a soft matrix, VEGF-C driven lymphangiogenesis was significantly blocked by the VEGFR-3 inhibitor but less extensively blocked by the VEGFR-2 inhibitor; in a stiff matrix, either the VEGFR-3 or VEGFR-2 inhibitors significantly blocked lymphangiogenesis, indicating that lymphangiogenic VEGFR-3 pathways mediate VEGF-C induced lymphangiogenesis the most in a soft matrix. VEGFR-2 can similarly contribute to lymphangiogenesis in a stiff matrix, showing VEGF-C mediated sprouting loses stiffness resilience under VEGFR-2 inhibition. Ultimately, VEGF-C/VEGFR-3 signaling has a greater impact on lymphangiogenesis in a compliant matrix, but VEGF-C/VEGFR-2 signaling mediates stiffness-resistant lymphangiogenesis in a stiff matrix. STATEMENT OF SIGNIFICANCE: The lymphatic system preserves fluid homeostasis by draining interstitial fluid. Lymphatic capillaries form new vessels through lymphangiogenesis across tissues spanning soft to stiff environments, yet how VEGF signaling functions under varying matrix stiffness remains unclear. Using a 3D lymphatics-on-a-chip model, we investigated lymphangiogenesis induced by VEGF-A, VEGF-C, and VEGF-C156S and assessed VEGFR-3 and VEGFR-2 inhibition. VEGF-C produced the strongest sprouting across all stiffness conditions; VEGF-A elicited weaker responses, and VEGF-C156S was effective only in soft matrices. In compliant matrices, VEGF-C-driven sprouting depended primarily on VEGFR-3. In stiff matrices, inhibition of either VEGFR-3 or VEGFR-2 significantly reduced lymphangiogenesis, revealing stiffness-dependent receptor contributions to VEGF-C-mediated sprouting, suggesting distinct therapeutic strategies for varying ECM stiffness in different organs and diseases.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pH-sensitive and ROS-responsive hydrogel enhanced by arginine-derived carbon dots for the diagnosis and treatment of infected wounds.","authors":"Xianli Wang, Jiajing Qiu, Zhengbin Dai, Jiacheng Li, Xiaoyu Li, Feiyue He, Jiaqi Dong, Huan Liu, Cheng Wang, Yi Shao, Chenglin Chu, Feng Xue, Li Tao, Liqu Huang, Jing Bai","doi":"10.1016/j.actbio.2026.10.009","DOIUrl":"10.1016/j.actbio.2026.10.009","url":null,"abstract":"<p><p>Effective repair of infected wounds requires both precise elimination of bacteria in the host and accelerated healing, yet strategies that integrate real-time diagnosis with targeted therapy remain scarce. Here, we synthesize L-arginine-derived carbon quantum dots (Arg‑CQDs) and incorporate them into a poly(ethylene glycol) diacrylate/carboxymethyl chitosan (PEGDA/CMCS) double-network hydrogel via free-radical polymerization. The resulting Arg‑CQDs-enhanced hydrogel functions as a sensitive pH-responsive optical sensor. Density functional theory (DFT) calculations reveal that under acidic conditions, Arg‑CQDs possess a smaller HOMO-LUMO gap and a larger oscillator intensity, favoring intense radiative electronic transitions. Under alkaline conditions, a larger gap and a smaller oscillator intensity promote dominant non‑radiative transitions. Consequently, the ultraviolet (UV)-excited luminescence intensity of the composite hydrogel decreases as pH increases, enabling visual assessment of infection via smartphone-based RGB color channel analysis. Moreover, the hydrogel exhibits microenvironment-selective pro-oxidant and antioxidant behavior. In bacterial environments, the positively charged Arg‑CQDs disrupt the electron transport chain and elevate reactive oxygen species (ROS) levels, achieving potent bactericidal activity. In cellular environments, they scavenge excess ROS through the up-regulation of GGT5 and Aldo-Keto reductase, thereby activating JAK2-STAT3/IL‑10 signaling to promote macrophage anti-inflammatory responses. In a rat model of infected wounds, this hydrogel achieves re‑epithelialization and vascularized wound closure within 14 days, outperforming commercial Ag⁺ dressings. This \"sense‑and‑act\" smart hydrogel represents a promising platform for the simultaneous diagnosis and treatment of infected wounds. STATEMENT OF SIGNIFICANCE: This work reports an Arg-CQDs-enhanced PEGDA/CMCS composite hydrogel that functions as a pH-responsive optical sensor, enabling smartphone‑based visual assessment of infection. DFT calculations reveal that acidic conditions promote intense radiative electronic transitions, whereas alkaline conditions favor weak non-radiative transitions, accounting for the pH‑dependent luminescence. Furthermore, the hydrogel exhibits microenvironment‑selective behavior. In bacterial niches, it elevates ROS levels to achieve potent sterilization. In cellular environments, it scavenges excess ROS and up-regulates GGT5 and Aldo‑Keto reductase, thereby activating JAK2-STAT3/IL-10 signaling to orchestrate anti-inflammatory responses. In a rat model of infected wounds, this \"sense‑and‑act\" hydrogel accomplishes complete re-epithelialization and vascularized closure within 14 days, outperforming commercial Ag⁺ dressings. Collectively, these findings establish a promising platform for the simultaneous diagnosis and treatment of infected wounds.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149119972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}