Acta Biomaterialia最新文献

{"title":"Revisiting the physical and chemical nature of the mineral component of bone","authors":"Furqan A. Shah","doi":"10.1016/j.actbio.2025.01.055","DOIUrl":"10.1016/j.actbio.2025.01.055","url":null,"abstract":"<div><div>The physico-chemical characteristics of bone mineral remain heavily debated. On the nanoscale, bone mineral resides both inside and outside the collagen fibril as distinct compartments fused together into a cohesive continuum. On the micrometre level, larger aggregates are arranged in a staggered pattern described as crossfibrillar tessellation. Unlike geological and synthetic hydroxy(l)apatite, bone mineral is a unique form of apatite deficient in calcium and hydroxyl ions with distinctive carbonate and acid phosphate substitutions (CHAp), together with a minor contribution of amorphous calcium phosphate as a surface layer around a crystalline core of CHAp. In mammalian bone, an amorphous solid phase has not been observed, though an age-dependent shift in the amorphous-to-crystalline character is observed. Although octacalcium phosphate has been postulated as a bone mineral precursor, there is inconsistent evidence of calcium phosphate phases other than CHAp in the extracellular matrix. In association with micropetrosis, magnesium whitlockite is occasionally detected, indicating pathological calcification rather than a true extracellular matrix component. Therefore, the terms ‘biomimetic’ or ‘bone-like’ should be used cautiously in descriptions of synthetic biomaterials. The practice of reporting the <em>calcium-to-phosphorus ratio</em> (Ca/P) as proxy for bone mineral maturity oversimplifies the chemistry since both Ca²⁺ and PO₄^3- ions are partially substituted. Moreover, non-mineral sources of phosphorus are ignored. Alternative compositional metrics should be considered. In the context of bone tissue and bone mineral, the term ‘mature’ must be used carefully, with clear criteria that consider both compositional and structural parameters and the potential impact on mechanical properties.</div></div><div><h3>Statement of significance</h3><div>Bone mineral exhibits a unique hierarchical structure and is classified into intrafibrillar and extrafibrillar mineral compartments with distinct physico-chemical characteristics. The dynamic nature of bone mineral, i.e., evolving chemical composition and physical form, is poorly understood. For instance, bone mineral is frequently described as “hydroxy(l)apatite”, even though the OH^- content of mature bone mineral is negligible. Moreover, the <em>calcium-to-phosphorus ratio</em> is often taken as an indicator of bone mineral maturity without acknowledging substitutions at calcium and phosphate sites. This review takes a comprehensive look at the structure and composition of bone mineral, highlighting how experimental data are misinterpreted and unresolved concerns that warrant further investigation, which have implications for characterisation of bone material properties and development of bone repair biomaterials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 1-16"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076417","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":"A promising strategy for ocular noninvasive protein delivery: The case in treating corneal neovascularization","authors":"Bangxun Mao ,&nbsp;Bojiao Tang ,&nbsp;Songping Yu ,&nbsp;Jia Ying ,&nbsp;Jing Wu ,&nbsp;Lina Lan ,&nbsp;Yanfang Wang ,&nbsp;Xingjie Zan ,&nbsp;Qinxiang Zheng ,&nbsp;Jun Li","doi":"10.1016/j.actbio.2025.02.006","DOIUrl":"10.1016/j.actbio.2025.02.006","url":null,"abstract":"<div><div>Current clinical treatment of corneal neovascularization (CNV), a leading cause of visual impairment worldwide, by a class of glucocorticoids suffers from the ineffective and numerous adverse effects. Bevacizumab (Beva), an anti-neovascularization protein, is a promising therapeutic option but limited by subconjunctival injection due to its poor penetration across ocular bio-barriers, which significantly reduces patient compliance and increases the risk of infection. Herein, a CmA@Beva nanomedicine was developed, based on the co-assembly of novelly designed peptide, (Cysteine-Histidine-Arginine)3, with Beva in the presence of Zn²⁺. The conditions for the formation of CmA and encapsulation of Beva in CmA were optimized, and the pH-responsive release of Beva and the protective effects of CmA@Beva on Beva were explored. In vitro and in vivo studies showed CmA@Beva exhibited good biocompatibility and demonstrated notable improvements in Beva retention time in the anterior eye segment. CmA@Beva eye drops could overcome corneal bio-barriers by opening ocular surface tight junctions and the endocytosis-lysosomal escape pathway, which together resulted in a therapeutic outcome on rat CNV superior to subconjunctival injection. The present study contributes to the development of a noninvasive protein drug delivery strategy for the treatment of CNV or other diseases of the eye anterior segment.</div></div><div><h3>Statement of significance</h3><div>Corneal neovascularization (CNV) has been recognized as the leading cause of vision impairment globally, affecting approximately 1.4 million people each year. Protein drugs have shown high specificity and low side effect in disease treatment compared to small molecule drugs. However, limited ability to cross ocular barriers remain a big challenge. Here, a nanomedicine (CmA@Beva) was employed to address this issue through exampling on an anti-neovascularization protein, bevacizumab (Beva). CmA@Beva enhances retention on the ocular surface and effectively delivers Beva across the epithelial barrier, and thus is much more effective than the commonly used subconjunctival injections used for treatment in the clinic. This may be a good strategy for non-invasive delivery of protein drugs for the treatment of anterior segment diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 307-320"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375074","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":"Corrigendum to “Cellular responses to thermoresponsive stiffness memory elastomer nanohybrid scaffolds by 3D-TIPS” [Acta Biomaterialia, 85, 2019, 157-171]","authors":"Linxiao Wu ,&nbsp;Adrián Magaz ,&nbsp;Elizabeth Maughan ,&nbsp;Nina Oliver ,&nbsp;Arnold Darbyshire ,&nbsp;Marilena Loizidou ,&nbsp;Mark Emberton ,&nbsp;Martin Birchall ,&nbsp;Wenhui Song","doi":"10.1016/j.actbio.2025.01.053","DOIUrl":"10.1016/j.actbio.2025.01.053","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 526-529"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400942","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":"A calcitonin gene-related peptide co-crosslinked hydrogel promotes diabetic wound healing by regulating M2 macrophage polarization and angiogenesis","authors":"Xiangyu Li ,&nbsp;Min Yi ,&nbsp;Ziyan Song ,&nbsp;Tianyi Ni ,&nbsp;Liying Tu ,&nbsp;Miao Yu ,&nbsp;Lantian Zhang ,&nbsp;Jingping Shi ,&nbsp;Weicheng Gao ,&nbsp;Qian Zhang ,&nbsp;Wei Yan","doi":"10.1016/j.actbio.2025.02.046","DOIUrl":"10.1016/j.actbio.2025.02.046","url":null,"abstract":"<div><div>Delayed diabetic wound (DBW) healing is a severe complication of diabetes, characterized notably by peripheral sensory neuropathy. The underlying mechanism of sensory nerves and DBW remain unclear. Here, we demonstrate the role of calcitonin gene-related peptide (CGRP) in regulating epithelialization and angiogenesis in DBW. Subsequently, we design and synthesis a gelatin methacryloyl (GelMA-CGRP) hydrogel that slowly releases CGRP, and evaluated its effect on promoting DBW healing. The results show that CGRP is abnormally downregulated in DBW, and CGRP ablation further delays DBW healing. This is due to the reduced M2 polarization and decreased angiogenesis in the absence of CGRP, whereas local application of GelMA-CGRP accelerates DBW healing. Mechanistic studies indicate that CGRP promotes M2 macrophage polarization by inhibiting the p53 signaling pathway and enhances endothelial cell function, thereby accelerating DBW healing. These findings suggest that CGRP could provide a novel therapeutic approach for diabetic wound treatment.</div></div><div><h3>Statement of significance</h3><div>Current methods for treating diabetic wounds have many limitations. Compared to conventional dressings, hydrogels combined with drugs or biological factors to promote diabetic wound healing have become an important research direction in recent years. This study reveals the key role of CGRP in the pathogenesis of diabetic wounds. The research found that CGRP promotes M2 macrophage polarization and angiogenesis by inhibiting the p53 signaling pathway, thereby promoting diabetic wound healing. We further utilized the carrier properties of GelMA hydrogel to develop a GelMA-CGRP hydrogel material that slowly delivers CGRP and effectively treats diabetic wounds. This material demonstrates strong biocompatibility and antimicrobial properties, offering a novel approach for the treatment of diabetic wounds.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 109-122"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532181","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":"Ribbon-like hypomineralization in human dental enamel","authors":"Máté Hegedűs ,&nbsp;Zsolt Kovács ,&nbsp;Lívia Vásárhelyi ,&nbsp;Ákos Kukovecz ,&nbsp;Levente Illés ,&nbsp;Noémi Szász ,&nbsp;Éva Mlinkó ,&nbsp;Noémi Rózsa Katinka ,&nbsp;Viktória Kovács Kis","doi":"10.1016/j.actbio.2025.02.064","DOIUrl":"10.1016/j.actbio.2025.02.064","url":null,"abstract":"<div><div>Human dental enamel is a uniquely hard and tough biological realization of the inherently brittle apatite crystal. In sound enamel both structure and chemistry are organically fine-tuned, while developmental disorders - such as hypomineralization - often lead to severe enamel alterations resulting in weaker mechanical performance and shorter lifetime as in case of molar-incisor hypomineralization (MIH) which has a global prevalence of 13.5 %. However, causes of the development of hypomineralization disorder remain unclear up to date. In the present paper, a new form of dental hypomineralization is reported for the first time. Structural and chemical alterations of dental enamel exhibiting a special ribbon-like hypomineralization (RLH) are compared to the characteristics of sound and MIH-affected teeth. Microporosity, mineral density and characteristic 3D macroscopic shape of the RLH affected volumes were captured by micro-CT analysis. On the submicron-scale, nanoporosity, unusual morphologies and reduced size of apatite nanocrystals have been revealed. These RLH specific features are coupled with a particular chemical fingerprint in Raman spectroscopy, which allows its clear separation from MIH affected and sound enamel. Based on these nanostructural features we conclude different failure mechanisms in the biochemical control during crystallization of the RLH and MIH enamel.</div></div><div><h3>Statement of significance</h3><div>Molar-incisor hypomineralization (MIH) is a developmental enamel disorder with up to 14 % prevalence, characterized by reduced mineral content, hypersensitivity, and post-eruptive enamel breakdown. The causes of the development of this disorder remain unclear up to date. In this study, we examine molars with hypomineralization in a ribbon-like macroscopic morphology. These molars show increased porosity, organic content, and reduced mineral content, while carbonate levels remain unchanged in both affected and unaffected areas, unlike MIH-affected enamel. Ribbon-like hypomineralized (RLH) enamel also features unusual apatite nanocrystal morphologies, including isometric crystals in the prism boundary zone and bean-shaped crystals with a soft central zone. Nanoscale analysis reveals RLH as a developmental anomaly distinct from MIH, offering novel insights into the biochemical controls of hypomineralization.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 281-292"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544896","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":"Sequential release of vascular endothelial growth factor and platelet-derived growth factor at the appropriate time for improved angiogenesis","authors":"Yu Liu ,&nbsp;Ying Luo ,&nbsp;Jianchen Zhang ,&nbsp;Lei Zhang ,&nbsp;Ying Guan ,&nbsp;Yongjun Zhang","doi":"10.1016/j.actbio.2025.03.010","DOIUrl":"10.1016/j.actbio.2025.03.010","url":null,"abstract":"<div><div>Sequential release of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was proposed to enhance therapeutic angiogenesis, however, it remains a challenge to accomplish distinct sequential release of the two proteins. More importantly, the appropriate timing of PDGF release remains an open question. Herein to solve these problems, a new time-controlled release system was designed in which tannic acid/Pluronic F127 (TA/F127) layer-by-layer (LBL) films were used as erodible coatings. The hydrogen-bonded TA/F127 films disintegrate in water at a constant rate. Therefore this system can not only achieve distinct sequential release of two proteins, but can finely control the lag time of the second protein by the TA/F127 coating thickness. In this way drug carriers for sequential release of VEGF and PDGF were prepared. Their angiogenic effects were evaluated using a mouse model of lower limb ischemia. Improved therapeutic efficiency was observed when VEGF and PDGF were sequentially released. More importantly, it was observed that the therapeutic efficiency first increased with increasing TA/F127 film thickness, reached a maximum, and then dropped with further increased TA/F127 film thickness. The results demonstrated that it is important to release PDGF at the appropriate time point to further improve angiogenesis. For the first time, the appropriate timing for PDGF application was determined to be 5–7 days after the application of VEGF.</div></div><div><h3>Statement of Significance</h3><div>It remains a challenge to accomplish distinct sequential release of VEGF and PDGF to enhance therapeutic angiogenesis. The appropriate timing for PDGF release is also an open question. In this study, a new time-controlled release system using a TA/F127 layer-by-layer film as an erodible coating was designed. Not only can distinct sequential release of VEGF and PDGF be achieved, but the lag time of PDGF release can also be finely controlled by the coating thickness. In this way, the appropriate timing for PDGF application was successfully determined.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 171-181"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588673","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":"Corrigendum to “Engineering a photosynthetic bacteria-incorporated hydrogel for infected wound healing” [Acta Biomaterialia, 140, 2022, 302-313]","authors":"Erman Zhao ,&nbsp;Huifang Liu ,&nbsp;Yaru Jia ,&nbsp;Tingshan Xiao ,&nbsp;Jiaxin Li ,&nbsp;Guoqiang Zhou ,&nbsp;June Wang ,&nbsp;Xiaohan Zhou ,&nbsp;Xing-Jie Liang ,&nbsp;Jinchao Zhang ,&nbsp;Zhenhua Li","doi":"10.1016/j.actbio.2025.02.018","DOIUrl":"10.1016/j.actbio.2025.02.018","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 541-543"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460714","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":"Additively manufactured biodegradable Zn-Mn-based implants with an unprecedented balance of strength and ductility","authors":"Chengcong Huang ,&nbsp;Yizhu Wang ,&nbsp;Fan Yang ,&nbsp;Yixuan Shi ,&nbsp;Shangyan Zhao ,&nbsp;Xuan Li ,&nbsp;Yuchen Lu ,&nbsp;Yuzhi Wu ,&nbsp;Jie Zhou ,&nbsp;Amir A. Zadpoor ,&nbsp;Wei Xu ,&nbsp;Yageng Li ,&nbsp;Luning Wang","doi":"10.1016/j.actbio.2025.02.047","DOIUrl":"10.1016/j.actbio.2025.02.047","url":null,"abstract":"<div><div>Additively manufactured (AM) biodegradable zinc alloys hold huge potential as promising candidates for bone defect and fracture repair, thanks to their suitable biodegradation rates and acceptable biocompatibility. However, the mechanical properties of AM zinc alloys developed so far, ductility in particular, fall short of the requirements for bone substitution. Here, we present Zn-1Mn and Zn-1Mn-0.4Mg alloy implants with unique microstructures, fabricated using laser powder bed fusion (LPBF). Notably, the LPBF Zn-Mn-Mg alloy exhibited an extraordinary balance of strength and ductility, with an ultimate tensile strength of 289 MPa, yield strength of 213.5 MPa, and elongation over 20 %, outperforming all previously reported AM zinc alloys. The simultaneously enhanced strength and ductility of the ternary alloy were attributed to the strong grain-refining effect of the Mg₂Zn₁₁ second phase and the synthetic strengthening caused by the dispersion of the MnZn₁₃ and Mg₂Zn₁₁ second phases inside the grains and at the grain boundaries. In addition, both alloys had similar rates of <em>in vitro</em> biodegradation (∼0.15 mm/year), properly aligned with the bone remodeling process, while also demonstrating favorable biocompatibility and upregulating multiple osteogenic markers. The Zn-Mn-Mg alloy showed even better osteogenic potential than the Zn-Mn alloy, owing to the addition of Mg. The combined attributes of the LPBF Zn-Mn-Mg ternary alloy indicated huge potential for its use as a bone repair material, especially for load-bearing bone fixation.</div></div><div><h3>Statement of significance</h3><div>The mechanical properties of previously developed additively manufactured biodegradable zinc alloys, especially ductility, have not met the requirements for bone repair. Using laser powder bed fusion (LPBF), we fabricated Zn-1Mn and Zn-1Mn-0.4Mg alloy implants with unique microstructures. The LPBF Zn-Mn-Mg alloy demonstrated an exceptional balance of strength and ductility, achieving a tensile strength of 289 MPa, yield strength of 213.5 MPa, and elongation over 20 %, surpassing all reported AM zinc alloys. This study is the first to produce a directly printed biodegradable alloy meeting the mechanical requirements for bone fixation devices without post-processing. Additionally, the alloy exhibited moderate a biodegradation rate and excellent biocompatibility, underscoring its potential for load-bearing bone repair applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"196 ","pages":"Pages 506-522"},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494878","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":"Dual cell-penetrating peptide-conjugated polymeric nanocarriers for miRNA-205–5p delivery in gene therapy of cutaneous squamous cell carcinoma","authors":"Cheng-Yu Lin ,&nbsp;Jia-You Fang ,&nbsp;Chien-Yu Hsiao ,&nbsp;Chiang-Wen Lee ,&nbsp;Abdullah Alshetaili ,&nbsp;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}

{"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 ,&nbsp;Yunbo Wang ,&nbsp;Pengqi Zhang ,&nbsp;Chenjie Gu ,&nbsp;Xianlei Zhao ,&nbsp;Xinghan Gong ,&nbsp;Xiaohang Yang ,&nbsp;Jianwei Pan ,&nbsp;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}