Acta BiomaterialiaPub Date : 2025-04-01DOI: 10.1016/j.actbio.2025.02.062
Tao Deng , Dong Chen , Fang Chen , Chaoqun Xu , Qiang Zhang , Min Li , Yashi Wang , Zhidi He , Man Li , Qin He
{"title":"Corrigendum to “Synergizing autophagic cell death and oxaliplatin-induced immunogenic death by a self-delivery micelle for enhanced tumor immunotherapy” [Acta Biomaterialia, 190, 2024, 548-559]","authors":"Tao Deng , Dong Chen , Fang Chen , Chaoqun Xu , Qiang Zhang , Min Li , Yashi Wang , Zhidi He , Man Li , Qin He","doi":"10.1016/j.actbio.2025.02.062","DOIUrl":"10.1016/j.actbio.2025.02.062","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 551-552"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588641","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}
Acta BiomaterialiaPub Date : 2025-04-01DOI: 10.1016/j.actbio.2025.02.061
Min Wang , Yunbo Wang , Pengqi Zhang , Chenjie Gu , Xianlei Zhao , Xinghan Gong , Xiaohang Yang , Jianwei Pan , Yongmei Xi
{"title":"Neutrophil-like cell membrane-coated metal-organic frameworks for siRNA delivery targeting NOX4 to alleviate oxidative stress in acute ischemic injury","authors":"Min Wang , Yunbo Wang , Pengqi Zhang , Chenjie Gu , Xianlei Zhao , Xinghan Gong , Xiaohang Yang , Jianwei Pan , Yongmei Xi","doi":"10.1016/j.actbio.2025.02.061","DOIUrl":"10.1016/j.actbio.2025.02.061","url":null,"abstract":"<div><div>Although reperfusion is the most effective treatment for acute ischemic stroke, it often results in serious secondary ischemia/reperfusion (I/R) injury due to oxidative stress. This oxidative stress primarily results from the overproduction of reactive oxygen species (ROS) during reperfusion which, in turn, is largely induced by high expression of NADPH oxidase 4 (NOX4). Inhibiting NOX4 gene expression has therefore been proposed as a direct approach to reduce ROS production and promote angiogenesis. Recognizing both the potential of siRNA-based therapies for selective gene silencing and the critical role of neutrophil-endothelial interactions during I/R injury, here we present a unique therapeutic approach where neutrophil-like cell membrane coated porous metal-organic framework nanoparticles are loaded with si<em>NOX4</em> (M-MOF-si<em>NOX4</em>) and designed to target damaged brain microvascular tissue. These then mitigate oxidative stress by suppressing NOX4 expression. Using an <em>in vitro</em> oxygen-glucose deprivation/re-oxygenation model, we demonstrate that M-MOF-si<em>NOX4</em> nanoparticles specifically bind to activated endothelial cells, effectively reducing NOX4 expression, decreasing both ROS production and cell apoptosis, and restoring cell viability. Use of an <em>in vivo</em> mouse model of middle cerebral artery occlusion further confirmed M-MOF-si<em>NOX4</em> nanoparticles to substantially alleviate brain damage and protect neurological function following ischemic stroke. Taken together, our study presents an innovative and effective siRNA-based strategy for reducing oxidative stress in ischemic stroke therapy.</div></div><div><h3>Statement of significance</h3><div>Ischemia/reperfusion (I/R) injury, a major complication of acute ischemic stroke, is primarily driven by oxidative stress due to the excessive production of reactive oxygen species (ROS). Current treatments targeting oxidative stress and cell death often lack specificity, leading to off-target effects. This study introduces an innovative nanoparticle-based therapy using neutrophil-like cell membrane-coated metal-organic frameworks (MOFs) to deliver siNOX4, an siRNA targeting NOX4, a key ROS-producing enzyme. This approach enhances targeted delivery, reduces ROS production and cell death, and significantly improves neurological recovery in stroke models. By overcoming the limitations of existing therapies, this strategy holds strong potential for revolutionizing ischemic stroke treatment and addressing other disorders related to oxidative stress.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 487-505"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538224","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}
Acta BiomaterialiaPub Date : 2025-04-01DOI: 10.1016/j.actbio.2025.01.063
Lianjiang Tan , Ran Huang , Xiaoqiang Li , Shuiping Liu , Yu-Mei Shen
{"title":"Corrigendum to “Controllable release of nitric oxide and doxorubicin from engineered nanospheres for synergistic tumor therapy” [Acta Biomaterialia 57, 2017, 498-510]","authors":"Lianjiang Tan , Ran Huang , Xiaoqiang Li , Shuiping Liu , Yu-Mei Shen","doi":"10.1016/j.actbio.2025.01.063","DOIUrl":"10.1016/j.actbio.2025.01.063","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 537-539"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392627","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}
Acta BiomaterialiaPub Date : 2025-04-01DOI: 10.1016/j.actbio.2025.02.056
Cheng-Yu Lin , Jia-You Fang , Chien-Yu Hsiao , Chiang-Wen Lee , Abdullah Alshetaili , Zih-Chan Lin
{"title":"Dual cell-penetrating peptide-conjugated polymeric nanocarriers for miRNA-205–5p delivery in gene therapy of cutaneous squamous cell carcinoma","authors":"Cheng-Yu Lin , Jia-You Fang , Chien-Yu Hsiao , Chiang-Wen Lee , Abdullah Alshetaili , Zih-Chan Lin","doi":"10.1016/j.actbio.2025.02.056","DOIUrl":"10.1016/j.actbio.2025.02.056","url":null,"abstract":"<div><div>Despite the potential of microRNAs (miRNAs) in suppressing tumorigenesis, the main challenges are achieving tumor-specific selectivity and efficient delivery into cancer cells. In this study, miR-205–5p-loaded polymeric nanoparticles conjugated with dual cell-penetrating peptides (CPPs) were designed for targeting and treating cutaneous squamous cell carcinoma (cSCC). The CPPs, R9, and p28, demonstrated high cell-penetrating/targeting abilities and antitumor activity. The anti-cSCC effect of the nanocarriers was examined using in vitro cellular 2D and 3D models and in vivo spheroid-xenografted murine models. The average size of the dual CPP-conjugated nanocarriers was 193 nm with a zeta potential of 5.7 mV. These nanocarriers were readily internalized by A431 cells, resulting in decreased proliferation compared to naked agomiR and nanoparticles with a single CPP. The nanocarriers induced cell cycle arrest in the G0/G1 stage. By loading the miR-205–5p mimic, the dual CPP-conjugated nanoparticles enhanced cell apoptosis threefold compared to the control, activating caspases and poly(ADP-ribose) polymerase (PARP). The wound healing assay demonstrated that the nanocarriers significantly inhibited the migration and invasion of cSCC cells. Additionally, the CPP-conjugated nanocarriers penetrated cSCC 3D spheroids, reducing spheroidal size and proliferation. In vivo studies demonstrated that the intratumoral CPP-conjugated nanocarriers achieved a 30 % reduction in tumor volume than the PBS control. The number of Ki67-positive cells in the nanocarrier-treated tumor decreased fivefold than the untreated tumors. The nanoparticulate agomiR (1 μM) exhibited no cytotoxicity towards normal keratinocytes. No significant toxicity was observed in the skin and peripheral organs following subcutaneous administration of the nanoparticles in healthy mice. These findings demonstrate that miR-205–5p mimic delivery via dual CPP-conjugated nanocarriers can promote efficient and safe cSCC regression.</div></div><div><h3>Statement of significance</h3><div>Cutaneous squamous cell carcinoma (cSCC) is a highly invasive skin malignancy with limited treatment options. This study introduces dual cell-penetrating peptide (CPP)-conjugated polymeric nanoparticles for delivering miR-205–5p, a tumor-suppressor microRNA, to cSCC cells. The nanosystem enhances cellular uptake, inhibits cell proliferation, and promotes apoptosis in both 2D and 3D tumor models. In vivo, the nanocarriers demonstrate significant antitumor efficacy with minimal toxicity, highlighting their potential as a targeted, non-invasive therapy. This research represents a promising advance in gene therapy for cSCC by combining nanotechnology and CPPs to address challenges in miRNA delivery and tumor targeting.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 332-349"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525425","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}
Acta BiomaterialiaPub Date : 2025-04-01DOI: 10.1016/j.actbio.2025.03.011
Fan Wu , Yu Qian , Chenglong Ge , Yang Zhou , Jing Yan , Xudong Li , Xun Liu , Yuheng Lei , Ziyin Zhao , Yuansong Wei , Junliang Zhu , Lichen Yin , Shanzhou Duan
{"title":"Oxygen/siRNA-carrying fluoro-nanosensitizers for radio-immunotherapy sensitization","authors":"Fan Wu , Yu Qian , Chenglong Ge , Yang Zhou , Jing Yan , Xudong Li , Xun Liu , Yuheng Lei , Ziyin Zhao , Yuansong Wei , Junliang Zhu , Lichen Yin , Shanzhou Duan","doi":"10.1016/j.actbio.2025.03.011","DOIUrl":"10.1016/j.actbio.2025.03.011","url":null,"abstract":"<div><div>The anti-tumor efficacy of radiotherapy (RT) is limited by the hypoxic and immunosuppressive tumor microenvironment (TME), which leads to RT resistance and failure in eradicating distant metastatic lesions. Herein, we developed a fluorinated nanosensitizer that could deliver both oxygen (O<sub>2</sub>) and ADAR1 siRNA into tumor cells to reinforce RT by alleviating hypoxia and immunosuppression. Fluorinated poly(β-amino ester) (fPBAE) was designed to complex ADAR1 siRNA (siADAR1) <em>via</em> electrostatic attraction and load O<sub>2</sub> due to the O<sub>2</sub>-dissolving capacity of fluoroalkyls. The formed nanocomplexes (NCs) facilitated robust cytosolic delivery into cancer cells after intratumoral injection, enabling efficient ADAR1 silencing to promote IFN-β release and enhance DC maturation and T cell infiltration. At the meantime, O<sub>2</sub> was released to alleviate tumoral hypoxia. As thus, NCs significantly enhanced the anti-tumor efficacy of RT and when further coupled with programmed death ligand-1 antibody, they effectively restrained the growth of both treated primary tumors and untreated distant tumors by eliciting robust systemic immune response. This study therefore reports an enlightened strategy for remodeling the immunosuppressive TME and sensitizing radio-immunotherapy.</div></div><div><h3>Statement of significance</h3><div>The hypoxic and immunosuppressive tumor microenvironment (TME) greatly limits the anti-tumor efficacy of radiotherapy (RT). To address this critical issue, a nano-sensitizer based on fluorinated poly(β-amino ester) (fPBAE) is herein developed to mediate efficient co-delivery of oxygen (O₂) and ADAR1 siRNA into tumor cells. ADAR1 silencing promotes DC maturation and T cell infiltration to reverse immunosuppression while the released O₂ alleviates hypoxia to sensitize RT. Thus, the nano-sensitizer remarkably enhances the anti-tumor efficacy of RT and elicits robust systemic immune response to eradicate primary and distant tumors when further coupled with PD-L1 antibody. This study provides a promising approach for RT sensitization and radio-immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 423-435"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588678","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}
Acta BiomaterialiaPub Date : 2025-04-01DOI: 10.1016/j.actbio.2025.03.055
Jenny Gao, Lucia Martin, Elise A. Loffet, Raphael Bertin, John F. Durel, Panagiotis Oikonomou, Nandan L. Nerurkar
{"title":"Material properties of the embryonic small intestine during buckling morphogenesis","authors":"Jenny Gao, Lucia Martin, Elise A. Loffet, Raphael Bertin, John F. Durel, Panagiotis Oikonomou, Nandan L. Nerurkar","doi":"10.1016/j.actbio.2025.03.055","DOIUrl":"10.1016/j.actbio.2025.03.055","url":null,"abstract":"<div><div>During embryonic development, tissues undergo dramatic deformations as functional morphologies are stereotypically sculpted from simple rudiments. Formation of healthy, functional organs therefore requires tight control over the material properties of embryonic tissues during development, yet the biological basis of embryonic tissue mechanics is poorly understood. The present study investigates the mechanics of the embryonic small intestine, a tissue that is compactly organized in the body cavity by a mechanical instability during development, wherein differential elongation rates between the intestinal tube and its attached mesentery create compressive forces that buckle the tube into loops. The wavelength and curvature of these loops are tightly conserved for a given species. Focusing on the intestinal tube, we combined micromechanical testing with histologic analyses and enzymatic degradation experiments to conclude that elastic fibers closely associated with intestinal smooth muscle layers are responsible for the bending stiffness of the tube, and for establishing its pronounced mechanical anisotropy. These findings provide insights into the developmental role of elastic fibers in controlling tissue stiffness, and raise new questions on the physiologic function of elastic fibers in the intestine during adulthood.</div></div><div><h3>Statement of Significance</h3><div>The functional form of adult organs is established during embryogenesis through the action of physical forces on tissues with precise material properties. Despite this, however, biological control of material properties during embryogenesis is poorly understood. Focusing on the small intestine, we identified elastic fibers - rather than oriented smooth muscle - as defining bending stiffness, prescribing the lengthy intestine to be buckled precisely into compact loops for proper placement within the body cavity. We revealed a role for elastin in storing elastic energy during cell contraction, highlighting a potential role for elastin in gut motility through the ability to resist cyclic deformations associated with peristalsis. These results provide insights into intestinal development and adult function, and highlight elastin's diverse roles during organogenesis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"198 ","pages":"Pages 257-266"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781929","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}
Acta BiomaterialiaPub Date : 2025-04-01DOI: 10.1016/j.actbio.2025.02.049
Grace M. Jeanpierre , Manuel K. Rausch , Samantha R. Santacruz
{"title":"Mechanical properties of fresh rhesus monkey brain tissue","authors":"Grace M. Jeanpierre , Manuel K. Rausch , Samantha R. Santacruz","doi":"10.1016/j.actbio.2025.02.049","DOIUrl":"10.1016/j.actbio.2025.02.049","url":null,"abstract":"<div><div>Studying brain tissue mechanics is critical for understanding how the brain's physical properties influence its biological functions. Non-human primates, such as rhesus monkeys, are a key translational model for human neuroscience research, yet their brain tissue mechanics remain poorly understood. We report the mechanical properties of rhesus monkey white (corona radiata, CR) and gray (basal ganglia, BG) matter during compression relaxation, tension relaxation, tension-compression cycling (strain = 0.15, n<sub>CR</sub> = 21, n<sub>BG</sub> = 14), and shear cycling (strain = 0.3, n<sub>CR</sub> = 17, n<sub>BG</sub> = 9). Compression relaxation yields short and long-term time constants of 1.13 ± 0.041 s and 26.3 ± 0.68 s for CR and 1.22 ± 0.046 s and 28.3 ± 0.70 s for BG. Tension relaxation yields short and long-term time constants of 1.10 ± 0.052 s and 28.2 ± 0.82 s for CR and 1.19 ± 0.052 s and 29 ± 1.3 s for BG. Tension-compression cycling yields elastic moduli (E₁, E₂, E₃) of 36 ± 3.8 kPa, 0.61 ± 0.096 kPa, and 9.3 ± 0.90 kPa for CR and 27 ± 4.8 kPa, 0.68 ± 0.092 kPa, and 8 ± 1.0 kPa for BG. Shear cycling yields E₁, E₂, and E₃ of 3.9 ± 0.77 kPa, 0.19 ± 0.034 kPa, and 3.1 ± 0.40 kPa for CR and 2.8 ± 0.52 kPa, 0.18 ± 0.058 kPa, and 3.2 ± 0.53 kPa for BG. Hysteresis areas are also captured during tension-compression and shear cycling. These findings extend the translatability of rhesus monkey models for neuroscience.</div></div><div><h3>Statement of Significance</h3><div>While rhesus monkeys are a valuable translational model in human neuroscience research, there is a huge gap in knowledge about rhesus monkey brain tissue mechanics. This study serves to increase our understanding of rhesus monkey brain tissue mechanics and is the first to report the stiffness, time constant, and hysteresis parameters for rhesus monkey brain tissue in compression, tension, and shear for both the corona radiata and basal ganglia. The data is available in an open-source format, allowing others to fit and validate their mechanical models.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 233-243"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525444","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}