Acta biomaterialia最新文献

{"title":"Matrix and cytoskeletal tension gate stretch-induced calcium signaling.","authors":"Patrick K Jaeger, Fabian S Passini, Barbara Niederoest, Maja Bollhalder, Sandro Fucentese, Jess G Snedeker","doi":"10.1016/j.actbio.2025.09.014","DOIUrl":"10.1016/j.actbio.2025.09.014","url":null,"abstract":"<p><p>The extracellular matrix (ECM) and mechanical loading shape cellular behavior, yet their interaction remains obscure. We developed a dynamic proto-tissue model using human tendon fibroblasts and live-cell calcium imaging to study how ECM and cell mechanics regulate mechanotransduction. Stretch-induced calcium signaling served as a functional readout. We discovered that ascorbic acid-dependent ECM deposition is essential for proto-tissue maturation and the recovery of stretch-induced calcium signaling at physiological strains. ECM synthesis and mechanical integration enhanced stretch sensitivity, reducing the strain needed to trigger a calcium response from ∼40 % in isolated cells to ∼5 % in matured proto-tissues. A strong correlation between tissue rupture and onset of calcium signaling indicates a mechanistic link to ECM damage. Disrupting ECM crosslinking, ECM integrity, cell alignment, or cytoskeletal tension reduced mechanosensitivity, demonstrating that stretch-induced calcium signaling depends critically on ECM-cytoskeleton integration and mechanics. Fundamentally, our work closely replicates stretch-induced calcium signaling observed in rodent tendon explants in an in vitro model and bridges the gap between cell-scale and tissue-scale mechanotransduction. STATEMENT OF SIGNIFICANCE: The dysregulation of the tendon extracellular matrix is central to tendon disease, with controlled mechanical loading via physical therapy as the only established treatment. Tendon cells repair and maintain the matrix based on mechanical demands, yet how they sense loading and how matrix or cytoskeletal mechanics influence this process remains unclear. Animal models are often impractical, and existing in vitro models lack physiological relevance. We developed a dynamic in vitro model that replicates load-induced calcium signaling, a physiological tendon cell response observed in rodent tendons, and show that matrix and cytoskeletal mechanics are key to load sensation. Anchored to a validated sensory response, our model enhances physiological relevance and offers a platform to study tendon degeneration and recovery mechanisms.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058837","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":"Dual-mode nitric oxide releasing vascular grafts for vascular homeostasis and antibacterial defense.","authors":"Yang Li, Jiayi Zhang, Zhen Xiang, Julin Wang, Siyu Ren, Jichun Zhao, Daihua Fu, Yunbing Wang","doi":"10.1016/j.actbio.2025.09.010","DOIUrl":"10.1016/j.actbio.2025.09.010","url":null,"abstract":"<p><p>Thrombosis, restenosis, and infection remain persistent challenges for vascular grafts, often leading to graft failure and severe clinical consequences. However, existing solutions are often limited by compromised functionality or impractical manufacturing complexity. Inspired by the spatiotemporal nitric oxide (NO) release patterns of endothelial (eNOS) and inducible (iNOS) synthases in native vasculature, we propose a dual-mode NO release strategy. Through facile incorporation of BNN6, a photoresponsive N-nitrosamine NO donor, into electrospun polycaprolactone (PCL), the graft achieves sustained eNOS-like NO release comparable to that of native endothelium, along with light-triggered iNOS-mimicking bursts for rapid bacterial eradication. The resulting PCL/BNN6 grafts exhibit tunable and long-lasting NO-releasing behavior. In vitro, eNOS-like NO release effectively suppresses platelet activation, inhibits smooth muscle cell adhesion, proliferation, and migration, and promotes macrophage polarization toward an anti-inflammatory phenotype. Upon light activation, iNOS-mimicking NO bursts efficiently eliminate both S. aureus and E. coli. In vivo, the grafts significantly attenuate inflammatory responses, and their light-activated antibacterial capability is validated in a simulated infection model. Overall, this bioinspired dual-mode NO release strategy establishes a dynamic interface between graft functionality and physiological demands, offering a promising solution to the multifactorial complications of vascular grafts through spatiotemporally controlled NO delivery. STATEMENT OF SIGNIFICANCE: Vascular grafts frequently fail due to thrombosis, restenosis, and bacterial infection. While nitric oxide (NO) plays a central role in preventing these complications, most NO-releasing materials suffer from short-lived or poorly controlled release. This study presents an eNOS/iNOS-inspired dual-mode NO-releasing graft that mimics native NO regulation-providing sustained baseline release for vascular homeostasis and light-triggered bursts for antibacterial defense. The system couples ease of fabrication with robust in vitro and in vivo performance, integrating antithrombotic, anti-hyperplastic, and antibacterial functions into a single platform. This work offers a promising strategy to enhance the long-term success of vascular implants and may inform future development of smart, responsive biomaterials.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058796","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":"Aligned hydrogels with continuous gradients for the design of complex bioactive niches.","authors":"Huaxiang Yang, Qiyuan Song, Yuesheng Huang, Liying Xiao, Gongwen Yang, Qiang Lu","doi":"10.1016/j.actbio.2025.09.008","DOIUrl":"10.1016/j.actbio.2025.09.008","url":null,"abstract":"<p><p>Continuous gradient signals play a vital role in maintaining tissue homeostasis and repairing damaged tissues. A challenge remains for biomaterials to design complex continuous gradients similar to the niches in vivo. Here, a simple but effective strategy is developed to introduce continuous gradient cues to aligned hydrogels by regulating the slow diffusion of nanosized aggregates. Beta-sheet enriched silk nanofibers were tuned to shorter nanoaggregates with ultrasonic treatment to change its diffusion activity. The nanoaggregates were arranged into the pre-designed discontinuous gradient patterns and incubated for several days to convert to continuous gradients through slow diffusion. The low-voltage electrical field was used to stabilize the gradients, following aligned structure formation. The resulting continuous gradients exhibited flexibility, high controllability, and versatility, enabling the formation of multiple complex gradients. Significantly better bioactivity was achieved for the hydrogels with continuous gradients, superior to that with discontinuous gradients. The rat full-thickness wound model indicated that the hydrogels with continuous SDF-1α gradients accelerated scarless wound healing and functional recovery, confirming the critical roles of the gradients in tissue regeneration. Our present study provides a universal platform to design complex niches with multiple continuous gradients, opening a new path for regenerative medicine and bionic organoids. STATEMENT OF SIGNIFICANCE: Both continuous gradient cues and alignment structures play crucial roles in tissue regeneration. Controlled diffusion behaviors were introduced to silk nanofiber systems with pre-designed discontinuous gradients to construct continuous gradients in the aligned hydrogels after electrical field treatment. The biomimetic hydrogels with alignment structure and flexible continuous gradients achieved improved simulation of complex microenvironment in vitro, which effectively regulated cell behaviors and accelerated tissue regeneration. The present work provides a platform to design bioactive materials and study cell-microenvironment interaction.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056594","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":"Progress in engineering functional cardiac tissues from iPSC-derived cardiomyocytes: advances in construction and applications.","authors":"Meiyi Huang, Sitian Liu, Xiong Zhou, Ling Wang, Yaobin Wu","doi":"10.1016/j.actbio.2025.09.011","DOIUrl":"10.1016/j.actbio.2025.09.011","url":null,"abstract":"<p><p>Engineered cardiac tissue (ECT) has emerged as a transformative platform for modelling cardiac diseases, drug screening, and regenerative therapies. Among the various strategies for ECT construction, cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) have gained prominence due to their capacity to overcome critical limitations of primary cardiomyocyte sources, such as species-specific differences, limited tissue availability, and ethical concerns. In this review, we present a comprehensive overview of recent advancements in the use of iPSC-CMs for ECT development. We begin by outlining current methodologies for differentiating iPSC into cardiomyocytes, followed by an evaluation of key tissue engineering approaches, including scaffold-based, scaffold-free, and biofabrication techniques, that are used to assemble functional cardiac constructs in vitro. Special attention is given to the comparative advantages and challenges of these platforms. We highlight emerging applications of iPSC-CM-based ECTs, focusing on heart-on-a-chip systems for disease modelling and high-throughput drug testing, as well as cardiac patches for myocardial repair. Finally, we highlight major challenges, such as iPSC-CM immaturity, poor vascularization, and limited electromechanical integration, and discuss emerging bioengineering strategies to overcome these barriers and advance the clinical translation of engineered cardiac tissues. STATEMENT OF SIGNIFICANCE: ECT is an increasingly sophisticated platform with significant potential for cardiac disease modelling, drug screening, and regenerative therapy. This review provides a comprehensive analysis of the emerging role of human iPSC-CMs in ECT development, with emphasis on advanced differentiation protocols, biomaterial-guided tissue assembly, and cutting-edge biofabrication strategies. By critically evaluating scaffold-based, scaffold-free, and bioprinting approaches, we offer an integrated perspective on the fabrication of functional cardiac constructs. In addition, we discuss translational applications-including heart-on-a-chip systems and myocardial patches-and examine key challenges such as iPSC-CM immaturity, limited vascularization, and suboptimal electromechanical coupling. This review presents a timely synthesis at the intersection of stem cell biology, biomaterials science, and tissue engineering, intended to guide the design of next-generation therapeutic cardiac tissues.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056619","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":"Design and fabrication of degradation resistant hydrogel optical fibers for potential long-term usage of photomedicine in deep-tissue.","authors":"Jiahao Zheng, Yue Yan, Yifan Li, Zeqi Zhang, Shijia Tang, Feimin Zhang, Kai Hou, Guoyin Chen, Meifang Zhu","doi":"10.1016/j.actbio.2025.09.009","DOIUrl":"10.1016/j.actbio.2025.09.009","url":null,"abstract":"<p><p>Hydrogel optical fiber has attracted attention in the fields of photomedicine in deep-tissue due to its biocompatibility, such as soft wet nature, tissue-like modulus, and low toxicity. Owing to its distinctive optical properties and the ease of crosslinking, PEGDA is commonly employed in the fabrication of hydrogel optical fibers with high light-guiding efficiency. However, due to the hydrolysis susceptibility of ester bonds, these hydrogel optical fibers tend to degrade rapidly in physiological environments, which may compromise their long-term functionality. Additionally, the development of a light transmission device that can operate long-term, efficiently and stably in the internal environment is expected to further promote the progress of photomedicine. In this work, we introduce a degradation-resistant hydrogel optical fiber (DRHOF) with high optical transmission. In the preparation process, we replace the ester bond in the polymer molecular chain with an amide bond with higher activation energy to achieve a longer degradation period. In addition, the sheath/core structured hydrogel fiber is prepared continuously by a coaxial needle, and the refractive index (RI) of the sheath/core spinning liquid is regulated to achieve low optical attenuation (0.12 ± 0.01 dB cm^-1 with 650 nm laser). It has lower cytotoxicity and causes less tissue inflammation after implantation than conventional polymer fibers. In terms of mechanical properties, its Young's modulus is adjustable between 0.08 MPa ∼ 0.41 MPa, which is similar to the modulus of the soft tissue. Thus, the DRHOF demonstrates the great potential being used as a highly effective tool for application in the field of photomedicine. STATEMENT OF SIGNIFICANCE: The fabricated DRHOF exhibits resistance to degradation and biocompatibility, which can maintain the structural integrity within the muscle tissue without causing severe inflammation for at least three months. The fabricated DRHOF shows a light attenuation of 0.12 ± 0.01 dB cm^-1 (λ=650 nm). After three months in a simulated human body environment, light attenuation remained at 0.156 dB cm^-1, showing that DRHOF is suitable for long-term photomedicine in deep tissues.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056599","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":"Engineering a multilayered 3D stromal barrier model for quantitative analysis of T cell infiltration and cytotoxicity.","authors":"Rii Morimura, Isana Nada, Yuka Mizue, Eiji Shinozaki, Naoya Fujita, Ryohei Katayama, Michiya Matsusaki, Yoshihiko Hirohashi, Shiro Kitano, Toshihiko Torigoe","doi":"10.1016/j.actbio.2025.09.012","DOIUrl":"10.1016/j.actbio.2025.09.012","url":null,"abstract":"<p><p>The development of immunocompetent three-dimensional (3D) culture systems is critical for advancing in vitro models that enable precise analysis of immune-tumor interactions. Here, we report a biomaterial-based method for engineering a multilayered 3D stromal construct using the cell-assembled viscous tissues (CAViTs) approach. This system enables spatial compartmentalization of cancer cells and stromal components, including fibroblasts and endothelial cells, thereby mimicking the tumor microenvironment (TME). When co-cultured with tumor-specific cytotoxic T lymphocytes (CTLs), the system permits quantitative analysis of T cell infiltration and cytotoxicity. Moreover, we constructed a cancer-associated fibroblast (CAF)-rich stroma to model immune exclusion. Drug screening using this model identified histone deacetylase (HDAC) inhibitors as agents capable of reducing stromal barrier function by downregulating ECM components, thereby enhancing T cell penetration. This platform provides a robust, tunable, and reproducible in vitro model for investigating immune-stroma dynamics and accelerating immunotherapeutic discovery. STATEMENT OF SIGNIFICANCE: We present a biomaterial-based method for engineering a multilayered 3D stromal construct using the cell-assembled viscous tissues approach. This system enables spatial compartmentalization of cancer cells and stromal components, closely mimicking the tumor microenvironment. Within this model, tumor cell killing by CTLs was successfully observed, resembling a \"hot tumor\" phenotype. Furthermore, we established a CAF-rich stroma to recapitulate immune exclusion. Drug screening using this platform revealed that HDAC inhibitors enhanced CTL-mediated cytotoxicity. Overall, this platform provides a robust, tunable, and reproducible in vitro model for investigating immune-stroma interactions and accelerating the discovery of novel immunotherapeutic strategies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056622","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":"Local viscoelasticity of denaturing spider silk dope is governed by dynamic hierarchical intermolecular interactions.","authors":"Karthik R Peddireddy, Hannah R Johnson, Gregory P Holland, Rae M Robertson-Anderson","doi":"10.1016/j.actbio.2025.09.005","DOIUrl":"10.1016/j.actbio.2025.09.005","url":null,"abstract":"<p><p>The remarkable mechanical properties of spider silk arise from the hierarchical self-assembly of intrinsically disordered spidroins-proteins that are highly sensitive to environmental conditions and mechanical stress. In vivo, spidroins form micelle-like supramolecular assemblies, believed to be critical for the silk spinning process. While bulk rheology studies have revealed viscoelastic behavior in native silk dope, the role of these supramolecular structures in shaping the local rheological response remains poorly understood. Here, we use optical tweezers microrheology to probe the frequency-dependent viscoelastic properties of spidroin solutions at varying concentrations under urea denaturing conditions. Denaturation partially disrupts higher-order assembly, allowing us to isolate and evaluate the mechanical contributions of pre-assembled structures. We identify a universal relaxation timescale of ∼0.5 s across all conditions, consistent with transient crosslinking interactions; as well as additional concentration- and time-dependent relaxation modes attributable to polymer entanglements and the gradual dissolution of large supramolecular assemblies. Unexpectedly, high-concentration solutions exhibit a diminished elastic plateau and more prominent high-frequency viscous regime compared to low-concentration solutions-behavior consistent with mesoscale phase separation and reduced entanglements. In contrast, less concentrated solutions remain entangled and miscible over time. These results reveal how pre-assembled structures tune the mesoscale rheology of spider silk dope, and demonstrate that microrheology can sensitively track structural transitions in complex, self-assembling protein solutions. STATEMENT OF SIGNIFICANCE: Intrinsically disordered spider silk proteins self-assemble into hierarchical biomaterials with unmatched strength and toughness. In their pre-assembled state, they are stored as a concentrated aqueous \"dope\" with viscoelastic behavior that is finely tuned for fiber formation, yet poorly understood. Here, we use optical tweezers microrheology to non-perturbatively probe the viscoelastic response of spider silk dope under denaturing conditions, isolating the mechanical contributions of pre-assembled structures. We uncover rich rheological features-including shear thinning, transient elastic plateaus, and a hierarchy of relaxation timescales-reflecting entanglement, crosslinking, and phase separation processes that depend on protein concentration and aging. This dynamic coupling between molecular organization and rheology provides key insight into how spiders convert disordered protein solutions into molecularly aligned, high-performance fibers.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042434","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":"Advances in optical imaging in the diagnosis of traumatic brain injury.","authors":"Qiufang Gong, Long Deng, Jiaxi Ru, Lutong Wen, Yanni Zhang, Zaifeng Chen, Xiaojie Wei, Jingbo Dong, Xuejiao Song, Chao Liang","doi":"10.1016/j.actbio.2025.09.004","DOIUrl":"10.1016/j.actbio.2025.09.004","url":null,"abstract":"<p><p>Traumatic brain injury (TBI), a leading cause of neurological disability, imposes a critical need for early and precise diagnosis due to its complex pathological heterogeneity, which directly impacts treatment efficacy and patient prognosis. Although conventional imaging techniques (e.g., CT, MRI) provide structural insights, their inherent limitations in molecular specificity, sensitivity for subtle lesions, and real-time dynamic monitoring necessitate the development of complementary approaches. Optical imaging, including fluorescence, bioluminescence, and photoacoustic imaging, have emerged as powerful tools, enabling non-invasive, real-time, and molecular-specific visualization of pathological cascades with high spatiotemporal resolution. In the field of TBI diagnosis, optical imaging has become a research hotspot. In this review, we systematically explore the mechanisms of optical imaging methods and discuss the latest advances in their use for TBI diagnosis and TBI biomarker identification, and further discusses the possible future development of optical imaging in early diagnosis of TBI. STATEMENT OF SIGNIFICANCE: (1) Highlights the limitations of current clinical imaging (CT/MRI) in detecting traumatic brain injury (TBI). (2) Showcases the unique advantages of optical imaging (e.g., fluorescence, photoacoustic, afterglow) for TBI diagnosis. (3) Introduces a timely, interdisciplinary review bridging nanomaterials, optical imaging, and TBI diagnostics.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042409","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":"Macrophage membrane-camouflaged dual drug-based biomimetic pH-responsive nanomedicine for synergistic antifungal-antioxidant therapy in oral candidiasis.","authors":"Kaiwen Bao, Yunfan Li, Yantao Li, Shuai Wu, Sheng Ni, Xiong Zhao, Ya Wang, Yi Liang, Qiao Chen, Xinmei Duan, Da Sun, Li Zhu, Wei Wu","doi":"10.1016/j.actbio.2025.09.003","DOIUrl":"10.1016/j.actbio.2025.09.003","url":null,"abstract":"<p><p>The escalating challenges of antifungal drug resistance, toxicity, and limited therapeutic strategies for oral candidiasis (OC) necessitate innovative treatment approaches. This study developed a pH-responsive baicalein-based nanocarrier by coupling baicalein with phenylboronic acid-functionalized polymethyl vinyl ether-maleic anhydride to encapsulate amphotericin B (AMB). The nanocarrier was further camouflaged with macrophage membranes, forming a biomimetic dual-drug nanoplatform (MPPB@A NPs) for synergistic antifungal-antioxidant therapy against OC. MPPB@A NPs leverage macrophage membrane coating to enhance active targeting of β-glucans on C. albicans, while borate ester bonds enable pH-responsive drug release at pH 5.5. MPPB@A NPs were demonstrated to effectively disrupt C. albicans biofilms and scavenge reactive oxygen species (ROS). In murine OC models, MPPB@A NPs significantly reduced oral fungal burden (11.17 % of the free AMB group) and alleviated oxidative stress. Subsequently, ROS-mediated inflammation was reduced. Furthermore, MPPB@A NPs exhibited the favorable biocompatibility, including hemolysis rates below 5 %, reduced cytotoxicity, and significantly lower nephrotoxicity compared to free AMB. Therefore, this study provides a promising strategy to overcome AMB toxicity and resistance while promoting the synergistic antifungal-antioxidant therapy for OC management. STATEMENT OF SIGNIFICANCE: Current oral candidiasis therapies face challenges of drug resistance and systemic toxicity. This study has the potential to address these limitations using a biomimetic nanoplatform combining macrophage membrane camouflage with a pH-responsive carrier, enabling targeted dual-drug delivery to infection sites. The membrane coating facilitates tissue accumulation, while pH-triggered release delivers amphotericin B within acidic fungal biofilms, disrupting Candida albicans. Baicalein, as a nanocarrier component, exhibits antioxidant and anti-inflammatory effects. This strategy synergistically combats fungal infection and associated oxidative stress damage while significantly enhancing drug biocompatibility and reducing systemic toxicity, offering a clinically translatable solution.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042454","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":"Development of oxidized hyaluronic acid based hydrogels for neuronal tissue engineering: Effects of matrix stiffness on primary neurons.","authors":"Markus Lorke, Sonja Kuth, Renato Frischknecht, Aldo R Boccaccini","doi":"10.1016/j.actbio.2025.09.007","DOIUrl":"10.1016/j.actbio.2025.09.007","url":null,"abstract":"<p><p>Due to the presence of hyaluronic acid (HA) in the human body, specifically the brain, HA-based hydrogels are promising candidates for neural tissue engineering applications. Providing the right mechanical and biological properties is essential to mimic the native tissue with the aim of achieving stimulatory effects and promoting regeneration. In this study, HA was oxidized using sodium metaperiodate (NaIO4) to produce oxidized hyaluronic acid (OHA). Hydrogels were then synthesized by crosslinking OHA with gelatin (GEL) through a Schiff base reaction, facilitated by microbial transglutaminase (mTG). The hydrogels were further modified to achieve different mechanical properties, and their long-term stability was investigated by varying the concentrations of OHA, GEL, and mTG. Compression tests as well as swelling/degradation studies confirmed an important influence of the precursor amount on the mechanical characteristics in these hydrogels. Increasing the amount of GEL and OHA at the same time led to a higher effective modulus and beneficial properties regarding long-term stability, and vice versa. Microstructural analyses proved the connection of the respective mechanical properties to the crosslinking density and mesh size. To investigate the applicability of the different hydrogel concentrations as ECM substitutes, three hydrogel compositions were selected and evaluated using E18 primary neurons. The experiments showed that the neuron survival rate as well as their development was optimal at lower ratios of the components with higher crosslinking amount and an intermediate stiffness (modulus) of ∼0.5 kPa. The results thus confirmed the versatility of the OHA-GEL system to be used as matrix in brain tissue engineering. STATEMENT OF SIGNIFICANCE: Neural damage poses a significant medical challenge, with the mechanics of native neural tissue still not fully understood. Hyaluronic acid (HA), a natural component of the brain's extracellular matrix, holds promise for neural tissue engineering. This study developed a hydrogel by oxidizing HA (OHA) and crosslinking it with gelatin (GEL) using a Schiff base reaction and microbial transglutaminase (mTG). By adjusting OHA, GEL, and mTG concentrations, the hydrogels were engineered to mimic brain tissue stiffness and maintain long-term stability. Compression and microstructural analyses linked crosslinking density and mesh size to mechanical properties. Testing with primary neurons demonstrated optimal survival and growth at intermediate stiffness, emphasizing the OHA-GEL system's potential for advancing neural repair.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042388","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}