Acta Biomaterialia最新文献

{"title":"Advances in photodynamic therapy and its combination strategies for breast cancer","authors":"Kainat Zahra ,&nbsp;Fei Deng ,&nbsp;Wei Deng ,&nbsp;Rui Sang","doi":"10.1016/j.actbio.2025.08.054","DOIUrl":"10.1016/j.actbio.2025.08.054","url":null,"abstract":"<div><div>Breast cancer remains one of the leading causes of cancer-related mortality worldwide, with treatment resistance and recurrence posing significant challenges to conventional therapies such as chemotherapy, surgery, and radiotherapy. Photosensitiser-assisted treatment strategies, particularly photodynamic therapy (PDT), have emerged as a promising alternative for breast cancer due to its targeted nature and minimally invasive approach. This review provides an overview of PDT as a treatment strategy for breast cancer. We begin by discussing the current therapeutic approaches and their limitations in breast cancer management. We then examine the principles and mechanisms underlying PDT, along with various delivery systems employed to enhance its efficacy, including liposomes, extracellular vesicles, gold nanoparticles and lipid-polymer hybrid nanoparticles. Furthermore, we highlight the recent advances in PDT-based combination therapies and their progress in clinical development. Finally, we identify the key remaining challenges and outline potential future research directions with a particular focus on AI integration, to improve therapeutic outcomes for breast cancer patients.</div></div><div><h3>Statement of significance</h3><div>Conventional treatments for breast cancer severely affect the therapeutic effects, particularly for aggressive and treatment-resistant subtypes. Photodynamic therapy (PDT) has emerged as a promising, minimally invasive alternative that enables selective tumour targeting. In the past three years, several reviews in this area have been published focusing on inorganic nanoparticles-based PDT and preclinical studies, which is a fairly narrow focus in the field of PDT for breast cancer. Our review addresses this gap by summarising the most recent developments in both preclinical and clinical applications of PDT for breast cancer, with a particular focus on its use in combination with other therapeutic modalities. We also explore future directions, including the integration of artificial intelligence to enhance treatment precision. This timely and broad-scope review is expected to attract wide interest from researchers, clinicians and industry stakeholders aiming to advance breast cancer therapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 125-140"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction mechanisms between antibiotics and calcium phosphate cements as pharmacologically active bone graft substitutes","authors":"Johannes K. Konrad ,&nbsp;Jevgenia Rudnik ,&nbsp;Ann-Christin Pöppler ,&nbsp;Katrin Hurle ,&nbsp;Uwe Gbureck","doi":"10.1016/j.actbio.2025.08.051","DOIUrl":"10.1016/j.actbio.2025.08.051","url":null,"abstract":"<div><div>Calcium phosphate cements (CPCs) are widely used as medical devices for treating bone defects due to their high biocompatibility and ease of clinical application. Their porous structure and low setting temperature make them suitable as drug delivery systems, enabling high local drug concentrations while minimizing systemic side effects. However, successful application requires predictable drug release and a thorough understanding of drug-cement interactions.</div><div>This study examined the interactions of vancomycin and gentamicin with three hydroxyapatite-forming CPCs. Investigations focused on the strength and nature of these interactions and the effects of drug addition on solubility, setting behavior, microstructure, rheological and mechanical properties of the cements, as well as drug release profiles, and antimicrobial activity.</div><div>Over 34 days, both antibiotics were largely released from all cements and maintained antimicrobial efficacy against typical bone infection pathogens. Release profiles varied significantly depending on cement type and antibiotic. Gentamicin notably prolonged setting times and influenced mineral phase development. In contrast, the effects on injectability, microstructure, final phase composition, and mechanical strength were minor.</div><div>These findings highlight the potential of antibiotic-modified CPCs for localized treatment of bone infections. Their clinical use appears promising, provided that the specific properties of each drug-cement combination are carefully considered.</div></div><div><h3>Statement of significance</h3><div>This study provides a comprehensive analysis of how the two clinically relevant antibiotics, vancomycin and gentamicin, interact with three distinct calcium phosphate cements that form hydroxyapatite in situ. By elucidating the nature and strength of drug-cement interactions, the work provides critical insights into how these interactions influence key material properties, including setting kinetics, phase evolution, microstructure, mechanical performance, and drug release behaviour. The findings are of high clinical relevance, as they inform the design of antibiotic-loaded mineral bone cements with predictable performance characteristics for the local treatment of osteomyelitis and other bone-related infections. The study underscores the need for individualized assessment of drug-carrier compatibility to ensure both material integrity and therapeutic efficacy, offering significant potential for improving patient outcomes in orthopaedic and trauma surgery.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 687-704"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable protein hydrogel microspheres with reactive oxygen species-responsive nitric oxide release for cardiac protection against ischemia/reperfusion injury","authors":"Houwei Zheng ,&nbsp;Fan Jia ,&nbsp;Ying Gao ,&nbsp;Kaicheng Deng ,&nbsp;Liyin Shen ,&nbsp;Chao Zheng ,&nbsp;Xin Xie ,&nbsp;Changyou Gao ,&nbsp;Tanchen Ren ,&nbsp;Yang Zhu","doi":"10.1016/j.actbio.2025.08.040","DOIUrl":"10.1016/j.actbio.2025.08.040","url":null,"abstract":"<div><div>Nitric oxide (NO) can alleviate cardiac ischemia/reperfusion injury with its anti-inflammatory, antioxidant, and angiogenic effects. However, local NO availability is limited due to its short half-life, reduced production, and consumption by excess reactive oxygen species (ROS) generated in injured myocardium. Here, we designed an injectable hydrogel microsphere system (WPI-H-N) based on acrylated whey protein (WPI), onto which phenylborate ester group was attached and served as a ROS-cleavable linker for 5-isosorbide mononitrate (ISMN), a NO donor. This injectable hydrogel microsphere system was designed to scavenge excess ROS, and release NO in response to oxidative stress in the niche in order to achieve on-demand NO release, reduce NO depletion by ROS, and prolong NO retention in the infarcted myocardium. In a rat I/R model, WPI-H-N protected cardiomyocytes from apoptosis, attenuated cardiac oxidative injury and improved angiogenesis in the infarcted myocardium. These results demonstrate that the combination of ROS scavenging and responsive NO release can simultaneously overcome the two major limitations of NO therapy, supporting the development of more efficient NO delivery strategies.</div></div><div><h3>Statement of Significance</h3><div>This study presents an injectable hydrogel microsphere system that synergistically scavenges reactive oxygen species (ROS) and enables on-demand nitric oxide (NO) release for cardiac protection against ischemia/reperfusion injury. Unlike existing NO delivery platforms, the ROS-responsive phenylborate ester linkage ensures spatiotemporally controlled NO release, minimizing premature consumption by ROS and secondary nitrosative stress. The microspheres’ dual functionality—simultaneously neutralizing oxidative stress and promoting angiogenesis—addresses critical limitations of conventional NO therapies. In vivo results demonstrate significant reductions in cardiomyocyte apoptosis, oxidative damage, and infarct size, alongside improved cardiac function and vascularization. This strategy offers a potentially translatable approach for local and controlled NO release to achieve cardiac repair. The work holds broad implications for ROS-related pathologies and precision therapeutic delivery in regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 176-192"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial uterus with fluidics-driven system using material-switching digital light processing 3D bioprinting","authors":"Soon Hee Kim ,&nbsp;Ji Won Heo ,&nbsp;Sudarshini Nath ,&nbsp;Moon Sik Oh ,&nbsp;Sol Kim ,&nbsp;Ji Seung Lee ,&nbsp;Kyunghee Kim ,&nbsp;Ok Joo Lee ,&nbsp;Suk Woo Lee ,&nbsp;In-Sun Hong ,&nbsp;Chan Hum Park","doi":"10.1016/j.actbio.2025.08.026","DOIUrl":"10.1016/j.actbio.2025.08.026","url":null,"abstract":"<div><div>Despite various attempts to replicate complex organ structures using 3D bioprinting technologies, the fabrication of a tissue-engineered endometrium with integrated vasculature remains a significant challenge in the field. In this study, we developed three bioinks by combining glycidyl methacrylate-modified GelMA (GelMAGMA) hydrogel precursor with endometrial stem cells, stromal cells, and endothelial cells to create a vascularized endometrial construct. Utilizing a one-step material-switching DLP 3D bioprinter capable of multi-material printing, we successfully fabricated an engineered endometrial construct with a vascular channel extending through both the functional and basal layers. The use of a perfusion culture system to circulate medium through the vascular network promoted cell activation, and estrogen treatment further validated the functionality of the construct. Additionally, <em>in vivo</em> subcutaneous implantation demonstrated the biocompatibility of the engineered tissue. This platform offers significant potential for tissue-engineered endometrial implants as well as research into various vascularized implantable tissues.</div></div><div><h3>Statement of significance</h3><div>This study aims to develop a vascularized tissue-engineered endometrium for use in disease research and tissue implantation. Key findings include the development of GelMAGMA-based bioinks, fabrication of a vascularized endometrial construct, validation of its functionality, and proof of biocompatibility. The results advance tissue engineering and personalized medicine, with significant implications for endometrial disease studies and vascularized tissue model development.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 382-404"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autologous platelet-rich plasma dual-network hydrogel promotes human endometrial regeneration","authors":"Xiao Chen ,&nbsp;Chengcheng Zhu ,&nbsp;Lu Wang ,&nbsp;Jialing Deng ,&nbsp;Zhuomin Wang ,&nbsp;Xiaolin Wu ,&nbsp;Haimin Tan ,&nbsp;Yiyuan Qu ,&nbsp;Bingbing Wu ,&nbsp;Yu Li ,&nbsp;Keren Cheng ,&nbsp;Jian Xu","doi":"10.1016/j.actbio.2025.08.038","DOIUrl":"10.1016/j.actbio.2025.08.038","url":null,"abstract":"<div><div>Intrauterine perfusion of platelet-rich plasma (PRP) is often used for the treatment of intrauterine adhesions (IUA). However, the further application of PRP is limited by its difficulty in attaching to the endometrial surface and its inability to release growth factors persistently. Therefore, in this study, a dual-network (DN) hydrogel was prepared by using hyaluronate gel as the matrix and cross-linked PRP, which was applied to the clinical treatment of IUA. The DN hydrogel showed non-swelling in PBS, and 28 % of DN hydrogel remained after 96 h in vivo, in which PDGF-BB and VEGF showed sustained linear releasement. Also, DN hydrogel could promote the proliferation of endometrial epithelial cells in human endometrial epithelial organoids, suggesting that PRP releasing PDGF-BB and VEGF in DN hydrogel played a role. After treatment of DN hydrogel in patients with moderate to severe IUA, the menstrual volume and subendometrial blood flow were significantly increased, the IUA score was significantly decreased, the number of endometrial epithelial glands was increased, and the expression levels of ERα, MKI67 and CD31 were increased after treatment. Further single-cell sequencing analysis of the endometrium before and after DN hydrogel treatment revealed that WNT signaling pathway was significantly enriched after treatment. Immunohistochemical results confirmed that the increased expression of SOX9 and LGR5 in human endometrial glands after treatment, and also DN hyrdrogel promoted SOX9 and LGR5 expression in organoids. In conclusion, this DN hydrogel can improve the therapeutic effect of PRP and promote endometrial repair and regeneration in patients.</div></div><div><h3>Statement of significance</h3><div>Dual-network hydrogels combined with Platelet-rich plasma (PRP) were successfully applied to human intrauterine adhesions and achieved the desired therapeutic effect. The PRP dual-network hydrogel enhanced the mechanical properties of PRP and promoted endometrial repair and regeneration in clinical patients probably by activating the WNT signaling pathway. This study proposes a clinically practical therapeutic strategy and provides a foundation for the utilization of PRP in the field of endometrial regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 222-241"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinic-in-a-dressing paradigm: Synchronized diagnosis and treatment in chronic wounds via hydrogel-nanofiber matrices","authors":"Liqin Tang ,&nbsp;Leru Zhang ,&nbsp;Zhihao Xu ,&nbsp;Mohammed Awad Abedalwafa ,&nbsp;Jun Wang ,&nbsp;Fujun Wang ,&nbsp;Lu Wang ,&nbsp;Yan Li","doi":"10.1016/j.actbio.2025.08.059","DOIUrl":"10.1016/j.actbio.2025.08.059","url":null,"abstract":"<div><div>Chronic wounds, a critical global health challenge, necessitate advanced solutions to address limitations in current care, such as subjective assessments, uncontrolled drug delivery, and poor integration of diagnosis and treatment. This study introduces a \"clinic-in-a-dressing\" system that combines in situ pH monitoring with dual-responsive (pH/enzyme) drug delivery for chronic wound management. The system integrates hyaluronic acid (HA)-encapsulated vancomycin-loaded zeolitic imidazolate framework (HZV) nanoparticles and fluorescein isothiocyanate (FITC) into a nanofiber-reinforced hydrogel sponge. HZV nanoparticles enable targeted antibiotic release in response to wound environments, while FITC provides pH-sensitive fluorescence for non-invasive infection monitoring. In vitro assays demonstrated pH-dependent vancomycin release (90.01 % at pH 5.5), enhanced antibacterial efficacy against <em>Staphylococcus aureus</em> (99.99 % inhibition) and <em>Escherichia coli</em> (96.12 % inhibition) via synergistic Zn²⁺ and vancomycin action. In vivo evaluation using a diabetic rat model showed accelerated wound healing with 93.38 % closure by day 14, compared to the control group, with reduced bacterial colonization by 98.46 %, and improved collagen deposition. The dressing’s real-time pH monitoring capability, validated <em>via</em> smartphone-based fluorescence analysis, correlating RGB values with wound status (R² = 0.987), enables dynamic wound assessment. This multifunctional system bridges diagnostic accuracy and therapeutic efficacy, offering a transformative solution for personalized chronic wound management.</div></div><div><h3>Statement of Significance</h3><div>Wound dressings are widely used for chronic wound repair but face limitations like subjective assessments, uncontrolled drug delivery, and poor integration of diagnosis and treatment. Our study introduces a new dressing that combines in situ pH monitoring with dual-responsive drug delivery, balancing diagnosis and treatment. The dressing integrates hyaluronic acid (HA)-encapsulated vancomycin-loaded zeolitic imidazolate framework (HZV) nanoparticles and fluorescein isothiocyanate (FITC) into a nanofiber-reinforced hydrogel sponge. HZV nanoparticles enable targeted antibiotic release in response to wound environments, while FITC provides pH-sensitive fluorescence for non-invasive infection monitoring. These insights enable the design of next-generation \"clinic-in-a-dressing\", improving clinical outcomes in chronic wound diagnosis and treatments.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 286-301"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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 ,&nbsp;Long Deng ,&nbsp;Jiaxi Ru ,&nbsp;Lutong Wen ,&nbsp;Yanni Zhang ,&nbsp;Zaifeng Chen ,&nbsp;Xiaojie Wei ,&nbsp;Jingbo Dong ,&nbsp;Xuejiao Song ,&nbsp;Chao Liang","doi":"10.1016/j.actbio.2025.09.004","DOIUrl":"10.1016/j.actbio.2025.09.004","url":null,"abstract":"<div><div>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.</div></div><div><h3>Statement of significance</h3><div>(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.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 105-124"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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 ,&nbsp;Hannah R Johnson ,&nbsp;Gregory P Holland ,&nbsp;Rae M Robertson-Anderson","doi":"10.1016/j.actbio.2025.09.005","DOIUrl":"10.1016/j.actbio.2025.09.005","url":null,"abstract":"<div><div>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.</div></div><div><h3>Statement of Significance</h3><div>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.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 467-477"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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 ,&nbsp;Yunfan Li ,&nbsp;Yantao Li ,&nbsp;Shuai Wu ,&nbsp;Sheng Ni ,&nbsp;Xiong Zhao ,&nbsp;Ya Wang ,&nbsp;Yi Liang ,&nbsp;Qiao Chen ,&nbsp;Xinmei Duan ,&nbsp;Da Sun ,&nbsp;Li Zhu ,&nbsp;Wei Wu","doi":"10.1016/j.actbio.2025.09.003","DOIUrl":"10.1016/j.actbio.2025.09.003","url":null,"abstract":"<div><div>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 <em>C. albicans</em>, while borate ester bonds enable pH-responsive drug release at pH 5.5. MPPB@A NPs were demonstrated to effectively disrupt <em>C. albicans</em> 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.</div></div><div><h3>Statement of Significance</h3><div>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.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 568-583"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Invasive cancer cells soften collagen networks and disrupt stress-stiffening via volume exclusion, contractility and adhesion","authors":"Irène Nagle ,&nbsp;Margherita Tavasso ,&nbsp;Ankur D. Bordoloi ,&nbsp;Iain A.A. Muntz ,&nbsp;Gijsje H. Koenderink ,&nbsp;Pouyan E. Boukany","doi":"10.1016/j.actbio.2025.08.036","DOIUrl":"10.1016/j.actbio.2025.08.036","url":null,"abstract":"<div><div>Collagen networks form the structural backbone of the extracellular matrix in both healthy and cancerous tissues, exhibiting nonlinear mechanical properties that crucially regulate tissue mechanics and cell behavior. Here, we investigate how the presence of invasive breast cancer cells (MDA-MB-231) influences the polymerization kinetics and mechanics of collagen networks using bulk shear rheology and rheo-confocal microscopy. We show that embedded cancer cells delay the onset of collagen polymerization due to volume exclusion effects. During polymerization, the cells (at 4% volume fraction) cause an unexpected time-dependent softening of the network. We show that this softening effect arises from active remodeling via adhesion and contractility rather than from proteolytic degradation. At higher cell volume fractions, the dominant effect of the cells shifts to volume exclusion, causing a two-fold reduction of network stiffness. Additionally, we demonstrate that cancer cells suppress the characteristic stress-stiffening response of collagen. This effect (partially) disappears when cell adhesion and contractility are inhibited, and it is absent when the cells are replaced by passive hydrogel particles. These findings provide new insights into how active inclusions modify the mechanics of fibrous networks, contributing to a better understanding of the role of cells in the mechanics of healthy and diseased tissues like invasive tumors.</div></div><div><h3>Statement of significance</h3><div>Understanding how cells influence tissue mechanics is crucial to unravel disease progression. While fibroblasts are known to stiffen tissues, the role of invasive cancer cells is less clear. Using collagen-based tissue models, we reveal that cancer cells unexpectedly soften the collagen matrix and disrupt its stress-stiffening response. By comparing active cells to passive particles and selectively blocking cell functions, we show that volume exclusion, adhesion, and contractility each play distinct roles in shaping tissue mechanics. This work sheds light on the physical impact of cancer cells on their environment, advancing our understanding on how cells dynamically alter the mechanical properties of tissues.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 433-444"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}