Acta Biomaterialia最新文献

{"title":"ROS-responsive hydrogel for bone regeneration: Controlled dimethyl fumarate release to reduce inflammation and enhance osteogenesis","authors":"Qiuxia Huang ,&nbsp;Yang Qu ,&nbsp;Mengchen Tang ,&nbsp;Kaiwen Lan ,&nbsp;Yilin Zhang ,&nbsp;Sishi Chen ,&nbsp;Weichang Li ,&nbsp;Lisha Gu","doi":"10.1016/j.actbio.2025.02.026","DOIUrl":"10.1016/j.actbio.2025.02.026","url":null,"abstract":"<div><div>Large bone defects, often arising from trauma or infection, pose a considerable therapeutic challenge due to their limited capacity for spontaneous healing, thus requiring bone graft materials for effective reparative procedures. The persistence of inflammation and elevated levels of reactive oxygen species (ROS) within these defect sites significantly impede bone regeneration process. Addressing this, an injectable hydrogel system with ROS-responsive functionality is developed, specifically tailored to the high ROS microenvironment characteristic of bone defects. This system incorporates hyaluronic acid functionalized with dopamine to introduce catechol moieties, and employs 4-formylphenylboronic acid as a crosslinking agent to form a dynamic hydrogel matrix (HAC) with carboxymethyl chitosan. The HAC hydrogel serves as a carrier for dimethyl fumarate (DMF), a compound with established anti-inflammatory and antioxidant effects, enabling its controlled release in response to ROS levels. Herein, we investigated the physicochemical properties of DMF loaded hydrogel (DHAC) by microstructure observation, <em>in vitro</em> degradation assay, self-healing test, injectability experiments, DMF drug release assay. Meanwhile, we systematically investigated its effects on inflammation, intracellular ROS, and osteogenesis. Consequently, the DHAC significantly reduced pro-inflammatory cytokines secreted by RAW264.7 cells and scavenged intracellular ROS in MC3T3 cells. This effect was accompanied by an augmentation in the osteogenic potential of MC3T3 cells and a promotion in the repair of cranial defects in rats. The DHAC, which exhibits anti-inflammatory, antioxidant, and osteogenic activity, hold great potential as an effective strategy for the management of large bone defects.</div></div><div><h3>Statement of significance</h3><div>Here, a novel dimethyl fumarate-loaded ROS-responsive hydrogel system was developed for effective treatment of large bone defects. Our findings demonstrated that the hydrogel not only promotes bone regeneration but also controls inflammation, addressing two critical challenges in bone healing. Comprehensive evaluations show significant improvements in bone formation and reduction of pro-inflammatory cytokines in animal models. Additionally, the hydrogel exhibits excellent reactive oxygen species scavenging ability, effectively modulating oxidative stress in the bone defect microenvironment. Findings suggest the hydrogel system may serve as a promising therapeutic strategy for clinical management of critical-sized bone defects.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 183-200"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional nanodrug for simultaneously combating chemoresistance and immunosuppression in Fusobacterium nucleatum-associated colorectal cancer","authors":"Xiaohui Li ,&nbsp;Mengdi Wu ,&nbsp;Yu Wu ,&nbsp;Youtao Xin ,&nbsp;Linran Gao ,&nbsp;Mahmoud Elsabahy ,&nbsp;Xuan Wang ,&nbsp;Jimin Zhang ,&nbsp;Xiongwei Qu ,&nbsp;Hui Gao","doi":"10.1016/j.actbio.2025.02.013","DOIUrl":"10.1016/j.actbio.2025.02.013","url":null,"abstract":"<div><div><em>Fusobacterium nucleatum</em> (<em>Fn</em>) infection in colorectal cancer (CRC) induces chemoresistance and creates an immunosuppressive tumor microenvironment, compromising the efficacy of conventional chemotherapy. To address these challenges, a multifunctional MPLO@HA nanodrug was developed by conjugating metformin (Met), oxaliplatin (OxPt), and lauric acid (LA) onto oligomethyleneimine, subsequently complexed with hyaluronic acid (HA). The MPLO@HA nanodrug is designed to target <em>Fn</em>-infected CRC, offering multiple mechanisms for enhanced therapeutic outcomes. The nanodrug features a multi-stimuli responsive structure that enables precise and controlled release at the tumor site, responsive to pH, glutathione, and hyaluronidase levels. The enhanced positive charge of self-assembled nanodrug combined with Met effectively eradicates both extracellular and intracellular <em>Fn</em>, overcoming <em>Fn</em>-induced chemoresistance. Furthermore, incorporating Met improves the efficacy of chemotherapy by sensitizing CRC cells to treatment. The immunomodulatory properties of the MPLO@HA nanodrug promote immunogenic cell death, repolarize macrophages from the M2 to the M1 phenotype, and reduce the levels of regulatory T cells and myeloid-derived suppressor cells. By integrating antimicrobial, chemotherapeutic, and immunomodulatory capabilities, the MPLO@HA nanodrug offers a promising and comprehensive approach to combating <em>Fn</em>-induced chemoresistance and immunosuppression in CRC. This strategy could also provide a foundation for developing treatments for other cancers associated with bacterial infections.</div></div><div><h3>Statement of significance</h3><div><em>Fusobacterium nucleatum</em> (<em>Fn</em>) infection in colorectal cancer (CRC) induces chemoresistance and creates an immunosuppressive tumor microenvironment, severely compromising treatment efficacy. Current therapies face challenges in addressing these issues due to the complex interactions between bacterial infection and tumor development. Our study introduces a multifunctional nanodrug, MPLO@HA, which integrates metformin, oxaliplatin, lauric acid, and hyaluronic acid into a multi-responsive nanodrug system. This nanodrug simultaneously combats bacterial infection, chemoresistance, and immunosuppression in <em>Fn</em>-associated CRC. MPLO@HA demonstrates synergistic effects by eradicating both extracellular and intracellular <em>Fn</em>, enhancing chemosensitivity, and modulating the tumor immune microenvironment. This comprehensive approach offers a promising strategy to overcome <em>Fn</em>-induced treatment barriers, potentially improving outcomes for patients with <em>Fn</em>-infected CRC and opening new avenues in bacteria-associated cancer therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 406-420"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375112","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":"Effect of binary mechanical environment on T cell function","authors":"Jatin Jawhir Pandit ,&nbsp;Abed Al-Kader Yassin ,&nbsp;Carlos Ureña Martin ,&nbsp;Guillaume Le Saux ,&nbsp;Angel Porgador ,&nbsp;Mark Schvartzman","doi":"10.1016/j.actbio.2025.02.029","DOIUrl":"10.1016/j.actbio.2025.02.029","url":null,"abstract":"<div><div>T cells, key players in the immune system, recognize antigens via T-cell receptors (TCRs) and require additional costimulatory and cytokine signals for full activation. Beyond biochemical signals, T cells also respond to mechanical cues such as tissue stiffness. Traditional <em>ex-vivo</em> mechanostimulating platforms, however, present a uniform mechanical environment, unlike the heterogeneous conditions T cells encounter <em>in-vivo</em>. This work introduces a mechanically-biphasic T-cell stimulating surface, with alternating soft and stiff microdomains, to mimic the complex mechanical signals T cells face. Results show that T cells exposed to this biphasic environment do not average the mechanical signals but instead respond similarly to those on a homogeneously soft surface, leading to lower activation compared to those on a stiff surface. Interestingly, long-term exposure to these patterns enhances the proliferation of central memory and effector T cell phenotypes, similar to stiff environments. These findings reveal the non-linear nature of T cell mechanosensing and suggest that mechanical heterogeneity plays a critical role in modulating T cell responses, providing new insights into T cell activation and potential implications for immunotherapies.</div></div><div><h3>Statement of significance</h3><div>This research offers a fresh perspective in T cell mehanosensing, an important yet underexplored aspect of immunity. While previous studies have demonstrated that T cells sense homogeneous mechanical environments <em>ex-vivo</em>, their ability to discern and respond to simultaneous mechanical cues–resembling the complexity of <em>in-vivo</em> conditions–remained unexamined. By designing a mechanically patterned surface with alternating soft and stiff microdomains, this study simulates the diverse mechanical landscape encountered by T cells <em>in-vivo</em>. The findings reveal that T cells predominantly respond to this pattern as they would to a uniformly soft environment. This insight, showing that mechanical signals shape T cell activation and promote specific phenotypes, enhances our understanding of T cell biology and points to new directions for immunotherapy development.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 83-93"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426823","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":"Matrix metalloproteinase-responsive melanin nanoparticles utilize live neutrophils for targeted high-risk plaque detection and atherosclerosis regression","authors":"Bo Fan ,&nbsp;Jie Hong ,&nbsp;Qian Wu ,&nbsp;Weiguang Shen ,&nbsp;Nan Hu ,&nbsp;Yang Xing ,&nbsp;Juan Zhang ,&nbsp;Wenwen Cai ,&nbsp;Ruiping Zhang","doi":"10.1016/j.actbio.2025.02.033","DOIUrl":"10.1016/j.actbio.2025.02.033","url":null,"abstract":"<div><div>Abrupt rupture of atherosclerotic plaque is the predominant contributor to acute cardiovascular events. It is of clinical importance to effectively identify and inhibit high-risk plaque progression. However, this remains a major challenge due to the inadequate targeting of theranostic agents to atherosclerotic lesions. Herein, we utilize live neutrophils to encapsulate melanin-based theranostics (termed MNP_pep-Gd) to enhance their plaque targeting, leveraging the inherent inflammatory tropism of neutrophils in atherosclerosis progression. The MNP_pep-Gd are fabricated using the water-insoluble gadolinium-chelated melanin nanoparticle modified with a detachable polyethylene glycol (PEG) segment <em>via</em> a matrix metalloproteinase (MMP)-cleavable peptide linker. Our work demonstrated that overexpressed MMP in high-risk plaques can induce an increase in particle size and prolonged retention time of the MNP_pep-Gd nanoprobe in lesions, making it a highly efficient contrast agent for magnetic resonance (MR) and photoacoustic (PA) dual-modal imaging atherosclerotic plaque. Concurrently, the melanin nanoparticles function as a therapeutic agent by scavenging multiple toxic reactive oxygen species (ROS), inhibiting the pro-inflammatory cytokines expression, and significantly reducing the foam cell formation. As a result, NE/MNP_pep remarkably alleviates atherosclerosis progression by a 24.7 % reduction for plaque area in ApoE^−/− mice. Immunohistochemical analysis confirmed that NE/MNP_pep treatment significantly reduced the macrophage content by 21.3 % and lipid burden by 15.6 % in plaques. In conclusion, our innovative nanoagent actively targets atherosclerotic sites, offers a noninvasive approach for identifying high-risk atherosclerotic plaques, and significantly contributes to the alleviation of lesion development in ApoE^−/− mice.</div></div><div><h3>Statement of significance</h3><div>Effective identification and inhibition of high-risk plaque progression hold clinical importance. However, it remains a major challenge due to the insufficient targeting of theranostic agents to plaques. Herein, a biomimetic nanoplatform is developed to actively target atherosclerosis plaque with the assistance of neutrophils, thereby minimizing off-target effects. Then, overexpressed MMP2 in high-risk plaques trigger the aggregation of hydrophobic Gd³⁺-labeled melanin nanoparticles, enhancing both MRI/PAI intensities for precise diagnosis. Additionally, the native antioxidant activity of melanin reduces inflammatory level, alleviates oxidative damage, and inhibits plaque progression in ApoE^−/− mice. This study offers valuable insights for accurate plaque assessment and provides effective guidance for subsequent management strategies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 496-508"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434533","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":"Zonal Characteristics of Collagen Ultrastructure and Responses to Mechanical Loading in Articular Cartilage","authors":"Jingrui Hu ,&nbsp;Keke Zheng ,&nbsp;Benjamin E. Sherlock ,&nbsp;Jingxiao Zhong ,&nbsp;Jessica Mansfield ,&nbsp;Ellen Green ,&nbsp;Andrew D. Toms ,&nbsp;C. Peter Winlove ,&nbsp;Junning Chen","doi":"10.1016/j.actbio.2025.01.047","DOIUrl":"10.1016/j.actbio.2025.01.047","url":null,"abstract":"<div><div>The biomechanical properties of articular cartilage arise from a complex bioenvironment comprising hierarchically organised collagen networks within the extracellular matrix (ECM) that interact with the proteoglycan-rich interstitial fluid. This network features a depth-dependent fibril organisation across different zones. Understanding how collagen fibrils respond to external loading is key to elucidating the mechanisms behind lesion formation and managing degenerative conditions like osteoarthritis. This study employs polarisation-resolved second harmonic generation (pSHG) microscopy to quantify the ultrastructural organisation of collagen fibrils and their spatial gradient along the depth of bone-cartilage explants under a close-to-<em>in vivo</em> condition. By combining with <em>in-situ</em> loading, we examined the responses of collagen fibrils by quantifying changes in their principal orientation and degree of alignment. The spatial gradient and heterogeneity of collagen organisation were captured at high resolution (1 μm) along the longitudinal plane of explants (0.5 mm by 2 mm). Zone-specific ultrastructural characteristics were quantified to aid in defining zonal borders, revealing consistent zonal proportions with varying overall thicknesses. Under compression, the transitional zone exhibited the most significant re-organisation of collagen fibrils. It initially allowed large deformation through the re-orientation of fibrils, which then tightened fibril alignment to prevent excessive deformation, indicating a dynamic adaptation mechanism in response to increasing strain levels. Our results provide comprehensive, zone-specific baselines of cartilage ultrastructure and micromechanics, crucial for investigating the onset and progression of degenerative conditions, setting therapeutic intervention targets, and guiding cartilage repair and regeneration efforts.</div></div><div><h3>Statement of significance</h3><div>Achieved unprecedented quantification of the spatial gradient and heterogeneity of collagen ultrastructural organisation at a high resolution (1 μm) along the full depth of the longitudinal plane of osteochondral explants (0.5 mm by 2 mm) under close-to-<em>in vivo</em> condition.</div><div>Suggested new anatomical landmarks based on ultrastructural features for determining zonal borders and found consistent zonal proportions in explants with different overall thicknesses.</div><div>Demonstrated that collagen fibrils initially respond by reorienting themselves at low strain levels, playing a significant role in cartilage deformation, particularly within the transitional zone. At higher strain levels, more collagen fibrils re-aligned, indicating a dynamic shift in the response mechanism at varying strain levels.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 104-116"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of the gelatin helix-to-coil transition through chain confinements at the polymer-protein interface and protein-protein interface","authors":"Woojin Choi,&nbsp;Jinkee Hong","doi":"10.1016/j.actbio.2025.02.003","DOIUrl":"10.1016/j.actbio.2025.02.003","url":null,"abstract":"<div><div>Gelatin is an essential material widely used in biomedical applications due to its characteristic temperature responsivity—helix-to-coil transition. However, the current helix-to-coil transition is limited by its single-step behavior and the difficulty in designing a specific onset temperature. In this study, we investigated the fundamentals of the helix-to-coil transition with a focus on gelatin chain mobility. We observed distinctive kinetics of the helix-to-coil transition, which is resilient and can actuate in multiple steps or with a controllable onset point. This was achieved by confining the gelatin chain with a hydrophilic polymer or gelatin itself. The confinement approach serves two purposes: first, it prevents excessive mobility of the generated coils, maintaining physical resilience after the helix-to-coil transition; second, the interfacial confinement between the polymer and gelatin, referred to as polymer-protein interface confinement, restricts the helix-to-coil transition, resulting in a multistep transition process. Additionally, strong confinement at the interface between gelatins of different origins, that is protein-protein interface confinement, shifts the onset temperature to a higher point. This fundamental comprehension of helix-to-coil transition could contribute to broadening the biomedical application potential of gelatin materials.</div></div><div><h3>Statement of significance</h3><div>Gelatin is essential in biomedical applications due to its characteristic temperature responsivity—helix-to-coil transition. Herein, we fundamentally investigated the distinctive kinetics of the helix-to-coil transition, which is resilient and can actuate in multiple steps or with a controllable onset point. This was achieved by confining the gelatin chain with a hydrophilic polymer or gelatin itself. The gelatin chain confinement prevents excessive mobility of the generated coils, maintaining physical resilience after the helix-to-coil transition. The interfacial confinement between the polymer and gelatin restricts the helix-to-coil transition, resulting in a multistep transition process. Additionally, strong confinement at the interface between gelatins of different origins shifts the onset temperature to a higher point.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 216-224"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367031","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":"DNA tetrahedron nanomedicine for enhanced antitumor and antimetastatic effect through the amplification of mitochondrial oxidative stress","authors":"Zixuan Chen ,&nbsp;Zhaoyan Tian ,&nbsp;Yafeng Wu ,&nbsp;Songqin Liu","doi":"10.1016/j.actbio.2025.02.011","DOIUrl":"10.1016/j.actbio.2025.02.011","url":null,"abstract":"<div><div>Amplifying mitochondrial oxidative stress by elevating reactive oxygen species (ROS) and reducing glutathione (GSH) levels proved highly effective in eradicating tumor cells and inhibiting metastasis. How to significantly amplify mitochondrial oxidative stress remains a challenge due to the hypoxic microenvironment and high level of GSH in the mitochondria. Herein, we smartly fabricated a multifunctional DNA tetrahedron nanomedicine (tDNA-TPP-AuNCs-BPQDs) for intracellular enzyme activated fluorescence imaging and amplified mitochondrial oxidative stress. The apurinic/apyrimidinic site (AP site) on the cantilever of DNA tetrahedron (tDNA) could be rapidly cleaved by apurinic/apyrimidinic endonuclease 1 (APE1), allowing for <em>in situ</em> fluorescence imaging of APE1 with high sensitivity and specificity. Gold nanoclusters (AuNCs) could continuously convert intracellular H₂O₂ to O₂ to alleviate the hypoxic conditions and adsorb intracellular GSH, thus the photodynamic therapy (PDT) effect of black phosphorus quantum dots (BPQDs) and AuNCs triggered a ∼10-fold and ∼3-fold increase in ROS generation compared to tDNA-TPP and tDNA-TPP-BPQDs, respectively. The elevated ROS and reduced GSH led to mitochondrial oxidative stress. In addition, the photothermal therapy (PTT) effect of the BPQDs and AuNCs further amplified the mitochondrial oxidative stress, which successfully induced immunogenic cell death (ICD) process and triggered a systemic antitumor immune response. The nanomedicine could render activation of fluorescence signal and anti-tumor therapeutic activity (34-fold higher than control) in tumor, thereby achieving effective tumor growth inhibition and antimetastatic effects.</div></div><div><h3>Statement of significance</h3><div>1. An effective mitochondrion targeting delivery system (tDNA-TPP-AuNCs-BPQDs) was developed for enhanced antitumor and antimetastatic effect through amplifying mitochondrial oxidative stress.</div><div>2. The multifunctional nanomedicine integrates tetrahedra DNA, Au NPs, TPP, and BP quantum dots to synergistically enhance cancer therapy effect through amplified mitochondrial oxidative stress. Additionally, an AP site segment was strategically incorporated into the tDNA structure for <em>in situ</em> fluorescence imaging of APE1 with high sensitivity and specificity in tumor cells.</div><div>3. The elevated ROS and reduced GSH amplify mitochondrial oxidative stress to induce ICD. The relieved hypoxic tumor microenvironment and induced ICD further stimulate a systemic antitumor immune response.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 378-389"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375107","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":"Engineered macrophage membrane-coated nanoparticles attenuate calcium oxalate nephrocalcinosis-induced kidney injury by reducing oxidative stress and pyroptosis","authors":"Xiaozhuo Ba ,&nbsp;Tao Ye ,&nbsp;Yu He ,&nbsp;Yonghua Tong ,&nbsp;Haojie Shang ,&nbsp;Jian Wu ,&nbsp;Wen Deng ,&nbsp;Zichen Zhong ,&nbsp;Xiaoqi Yang ,&nbsp;Kangyang Wang ,&nbsp;Yabin Xie ,&nbsp;Kehua Jiang ,&nbsp;Xiaolin Guo ,&nbsp;Kun Tang","doi":"10.1016/j.actbio.2025.02.021","DOIUrl":"10.1016/j.actbio.2025.02.021","url":null,"abstract":"<div><div>Kidney stones are characterized by a high incidence and recurrence rate, leading to kidney injury, which in turn accelerates stone formation and deposition. Increasing evidence have demonstrated that oxidative stress and cell pyroptosis play important role in the calcium oxalate (CaOx) stones induced kidney injury. Currently, treatments related to oxidative stress and inflammation associated with kidney stones are still relatively limited. Here, we designed engineered macrophage cell membrane-coated hollow mesoporous manganese dioxide nanoparticles loaded with NLRP3 inhibitors Mcc950 (KM@M@M). KM@M@M NPs were modified with Kim-1 targeting peptides on M2-polarized macrophage membranes to achieve better targeted delivery to injured kidney tubules. Compared with traditional drugs, KM@M@M NPs reduce systemic toxicity through targeted drug delivery to the kidneys. <em>In vivo</em> and <em>in vitro</em> results demonstrate that KM@M@M NPs reduces the activation of the NLRP3 inflammasome in renal tubular epithelial cells by scavenging ROS, thereby downregulating gasdermin D cleavage and the production of inflammatory cytokines, ultimately inhibiting cell pyroptosis. In addition, bioinformatic analysis revealed that KM@M@M NPs protect against CaOx induced kidney injury via suppressing the NLRP3/GSDMD pathway. This article extending the application of engineered cell membrane-based biomimetic nanotechnology, and providing a promising strategy for dual protection in CaOx stones induced kidney injury.</div></div><div><h3>Statement of significance</h3><div>Currently, apart from invasive surgery, there are few pharmacological therapies for CaOx-induced renal injury. This study presents a new strategy using engineered macrophage cell membrane-coated hollow mesoporous manganese dioxide nanoparticles (KM@M@M) to target and treat calcium oxalate (CaOx)-induced kidney injury. The nanoparticles effectively scavenge reactive oxygen species (ROS) and inhibit NLRP3 inflammasome activation, preventing pyroptosis and kidney damage. By delivering NLRP3 inhibitors directly to injured renal tubules, KM@M@M NPs reduce inflammation and stone deposition. This work demonstrates the potential of biomimetic nanotechnology for targeted treatment, offering a promising approach to prevent CaOx-induced renal injury and enhance therapeutic outcomes in kidney stone disease.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 479-495"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416523","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":"Rapid synthesis of degradable ester/thioether monomers and their incorporation into thermoset polyurethane foams for traumatic wound healing","authors":"Natalie Marie Petryk,&nbsp;Leo Saldanha,&nbsp;Shawn Sutherland,&nbsp;Mary Beth B. Monroe","doi":"10.1016/j.actbio.2025.02.027","DOIUrl":"10.1016/j.actbio.2025.02.027","url":null,"abstract":"<div><div>Polyurethane (PUr) foam hemostatic dressings are highly effective at controlling bleeding in traumatic wounds, but their traditionally slow degradation rate requires dressing removal, which could result in wound rebleeding. Incorporating degradable linkages into the PUr network can provide a biodegradable dressing that could be left in place during healing, eliminating rebleeding upon removal and providing scaffolding for new tissue ingrowth with no remains of the applied dressing after healing. In this work, a library of degradable PUr foams was synthesized from degradable monomers based on hydrolytically labile esters and oxidatively labile thioethers using rapid click-chemistry reactions. In a twelve-week <em>in vitro</em> degradation study in 3% hydrogen peroxide and 0.1 M sodium hydroxide, incorporation of degradable monomers resulted in significantly increased PUr foam mass loss, offering biodegradable foam dressings that could better match the rate of traumatic wound healing. Changes to foam chemical, mechanical, thermal, and physical properties throughout degradation were also analyzed. Furthermore, the degradable PUr foams had increased platelet interactions, which could improve foam-induced clotting for a more effective hemostatic dressing. Overall, a biodegradable PUr foam hemostatic dressing could significantly improve healing outcomes in traumatic wounds.</div></div><div><h3>Statement of significance</h3><div>A simple, solvent-free, rapid synthesis technique was developed to provide degradable polythiol monomers for use in polyurethane synthesis. The degradable monomers were incorporated into hemostatic polyurethane foams to provide materials with tunable degradation rates within clinically-relevant time frames. The resulting foams and their degradation byproducts were cytocompatible and hemocompatible, and foams made with the new degradable monomers had enhanced blood clotting, enabling their future use as hemostatic dressings.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 266-282"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning insights into calcium phosphate nucleation and aggregation","authors":"Jing Wang ,&nbsp;Xin Wang ,&nbsp;Dingguo Xu","doi":"10.1016/j.actbio.2025.02.036","DOIUrl":"10.1016/j.actbio.2025.02.036","url":null,"abstract":"<div><div>In this study, we utilized machine learning interatomic potentials (MLIPs) to investigate the nucleation mechanisms of calcium phosphate, a critical component of bone and teeth. Our analysis encompassed the process from pre-nucleation stage to the growth of amorphous calcium phosphate (ACP) in solution. We observed fluctuations in free calcium ion concentration and tracked the formation of uniform clusters in the early nucleation phases, confirming the existence of pre-nucleation clusters (PNCs). The PNCs are characterized by the composition Ca₂[(PO₄)_1.6(HPO₄)(H₂PO₄)_0.4] and predominantly exhibit a triangular structure formed by phosphate groups. This structure is not only the core of the short-range ordered units in ACP but also exhibits the structural characteristics of the fundamental building blocks of HAP. Importantly, these clusters interact dynamically with water molecules through hydrogen bonding and proton exchange, which is essential for their stability and growth. The gradual growth of these clusters occurs via ion attachment and cluster adsorption. This work provides insights into calcium phosphate mineralization, with implications for materials science and biomedical engineering, particularly in biomaterial synthesis. The application of MLIPs demonstrates a high-accuracy, efficient approach for simulating complex systems may advance our understanding of crystallization and biomineralization processes.</div></div><div><h3>Statement of significance</h3><div>Calcium phosphate nucleation is crucial in biological mineralization and the synthesis of biomaterials, serving as a key aspect in the design of hydroxyapatite (HAP)-based biomaterials. However, the mechanisms of early nucleation remain unclear due to the complex ion-water interactions, which lead to rapid nucleation rates and small cluster sizes. This study combines MLIP with MD simulations to explore the nucleation process of calcium phosphate, revealing the transition from pre-nucleation to the formation of ACP. It clarifies the relationship between PNCs and the crystalline structure of HAP. This work addresses the knowledge gap regarding early-stage calcium phosphate nucleation and highlights the potential of MLIP in simulating complex ionic solutions, laying a solid foundation for AI-guided research in biological and biomedical materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 547-558"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470253","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}