Acta Biomaterialia最新文献

{"title":"Matrix metalloproteinases accelerate pericellular matrix breakdown and disrupt mechanotransduction in osteoarthritis","authors":"Jule Nieuwstraten , Rosa Riester , Ulf Krister Hofmann , Farshid Guilak , Marina Danalache","doi":"10.1016/j.actbio.2025.02.034","DOIUrl":"10.1016/j.actbio.2025.02.034","url":null,"abstract":"<div><div>The pericellular matrix (PCM) is a specialized, narrow matrix surrounding each chondrocyte in articular cartilage, together constituting the chondron - the fundamental metabolic and functional unit of cartilage. The PCM plays a vital role in mediating biomechanical and biochemical signals essential for chondrocyte function. In osteoarthritis (OA), a chronic joint disorder characterized by progressive cartilage degradation, the PCM is one of the earliest sites of catabolic degradation, primarily driven by matrix metalloproteinases (MMPs). This study aims to investigate the functional relationship between PCM degradation and chondrocyte mechanosignaling, with an emphasis on MMP-driven changes in mechanotransduction in osteoarthritic cartilage.</div><div>Human chondrons (N = 64) were incubated with MMP-2, MMP-3, and MMP-7, and structural changes were assessed histologically by evaluating perlecan and collagen type VI. Cellular elasticity was measured using atomic force microscopy (AFM), and mechanically evoked intracellular Ca2+ transients were assessed via AFM single-cell indentations (500 nN).</div><div>All three MMPs induced pronounced catabolic effects on the PCM structure, showing distinct impacts on collagen type VI and perlecan, as well as on the biomechanical properties (p < 0.001). MMP-driven alterations in PCM integrity significantly reduced the Ca2+ transients of chondrons in response to mechanical stimuli (p < 0.001). While TRPV4 activation was elevated in intact chondrons, PIEZO channels were involved in mechanotransduction in both healthy and MMP-treated chondrons. In osteoarthritic stages, the mechanotransduction dynamics shifted significantly towards PIEZO channels.</div><div>This study elucidates the interplay between MMP-mediated PCM degradation, structural-functional dynamics, and chondrocyte mechanotransduction, underscoring the critical role of the PCM in maintaining normal chondrocyte functionality and mechanosensing.</div></div><div><h3>Statement of significance</h3><div>Osteoarthritis (OA) is a prevalent degenerative joint disease affecting millions worldwide. Central to its pathology is the degradation of the pericellular matrix (PCM) by matrix metalloproteinases (MMPs), which disrupts chondrocyte mechanotransduction, altering cellular responses to mechanical stimuli. This study explores the impact of MMP-2, MMP-3, and MMP-7 on PCM structure and chondrocyte mechanosensing. Our results reveal that MMP-induced degradation significantly compromises PCM structural integrity, leading to altered mechanotransduction dynamics in chondrocytes. Degradation specifically redirects the primary function of ion channels from TRPV4 to PIEZO channels in cells impacted by MMPs. This highlights the interplay between MMP-mediated PCM degradation, chondrocyte mechanotransduction and as thus structural-functional dynamics, underscoring the critical role of the PCM in maintaining normal chondrocyte functionality and mechanosensing.","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"195 ","pages":"Pages 73-82"},"PeriodicalIF":9.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434552","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":"Multiphysics modelling of the impact of skin deformation and strain on microneedle-based transdermal therapeutic delivery","authors":"Wenting Shu ,&nbsp;Sean Kilroy ,&nbsp;Aisling Ní Annaidh ,&nbsp;Eoin D. O'Cearbhaill","doi":"10.1016/j.actbio.2024.12.053","DOIUrl":"10.1016/j.actbio.2024.12.053","url":null,"abstract":"<div><div>Microneedle patches (MNs) hold enormous potential to facilitate the minimally-invasive delivery of drugs and vaccines transdermally. However, the micro-mechanics of skin deformation significantly influence the permeation of therapeutics through the skin. Previous studies often fail to appreciate the complexities in microneedle-skin mechanical interactions. This may impede the accuracy of MNs pre-clinical assessments. Here, we develop a multiphysics finite element model which simulates the biomechanics of microneedle skin penetration <em>and</em> the subsequent permeation of therapeutics. Employing the aqueous pore path hypothesis, we consider how strain (induced through the insertion of a MN), affects pore geometry in the skin and therefore the diffusion of therapeutics. Our models show that considering the insertion-induced skin deformation alone reduces the transdermal permeation of insulin by 25 %, while considering the effect of strain can reduce the overall permeation by a further 45 % over 24 h. Our model also indicates that once the mechanical strain is removed i.e. through removal or dissolution of the array, the permeation through the skin will recover. Furthermore, our results indicate that the delivery of high molecular weight compounds may be most susceptible to strain-induced changes in drug permeation. These findings could have significant implications for the preferred type of microneedle administration when targeting, for example, intradermal or transdermal delivery.</div></div><div><h3>Statement of significance</h3><div>This manuscript presents an advanced computational model of microneedle insertion into human skin. Here, we adopt a multiphysics modelling strategy, where we predict the influence of microneedle insertion on skin deformation and strain and how that influences subsequent therapeutic permeation through the skin. Our model predicts that whether or not the microneedle remains <em>in situ</em>, the resultant change in tissue deformation and strain has a major impact on how quickly the therapeutic diffuses through the skin. This has important implications for transdermal device design, administration strategies and protocols and associated clinical studies, where either intradermal or transdermal therapeutic delivery is being targetted.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 233-245"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878934","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":"Rho kinase inhibitor Y-27632 and dual media culture approach promote the construction and transplantation of rabbit limbal epithelial cell sheets via cell spheroid culture and auto-bioprinting","authors":"Peiyuan Wang ,&nbsp;Shuhao Shen ,&nbsp;Yonglong Guo ,&nbsp;Jixing Cao ,&nbsp;Deliang Zhu ,&nbsp;Mengyuan Xie ,&nbsp;Quan Yu ,&nbsp;Zekai Cui ,&nbsp;Shiwei Liu ,&nbsp;Jun Zhang ,&nbsp;Jiansu Chen","doi":"10.1016/j.actbio.2025.01.022","DOIUrl":"10.1016/j.actbio.2025.01.022","url":null,"abstract":"<div><div>The shortage of corneal donors and the limitations in tissue engineering grafts, such as biocompatibility and mechanical properties, pose significant challenges in corneal transplantation. Here, for the first time, we investigate the effect of Rho kinase inhibitor Y-27632 and a dual media culture approach, including proliferative media (M1) and stabilizing media (M2), on rabbit limbal epithelial stem cells (LESCs), aiming to explore the feasibility of constructing corneal cell sheets in vitro through auto-bioprinting and assessing their corneal wound healing capacity in vivo. Y-27632 has primarily demonstrated significantly enhanced LESCs growth, proliferation, and reduced apoptosis. The dual media culture approach combined with Y-27632 improved LESCs proliferation while maintaining stemness. In spheroid culture, Y-27632 decreased cell death and promoted proliferation. Immunofluorescent staining and RNA sequencing revealed upregulation of genes related to tight junctions and cell adhesion and downregulation of genes associated with aging and cell cycle. Using a bioprinter, LESC spheroids were auto-bioprinted onto a custom-made curved collagen membrane, creating a bioactive, transplantable, tissue-engineered anterior corneal sheet. Anterior superficial corneal transplantation with these LESC sheets significantly accelerated epithelial wound healing in rabbit limbal stem cell deficiency (LSCD) models. Overall, the integration of Y-27632, dual-media culture, and spheroid cell culture led to the development of a highly bioactive and therapeutically promising bio-ink derived from LESCs. Auto-bioprinting these LESC spheroids produced a bioactive, transplantable corneal cell sheet, presenting a promising therapeutic option for LSCD.</div></div><div><h3>Statement of Significance</h3><div>The renewal and wound healing of the corneal epithelium are essential for maintaining normal vision and refractive function. Limbal stem cell deficiency (LSCD) is a major cause of blinding keratopathy, and current treatment options are limited. In this study, for the first time, we developed a highly bioactive and therapeutically potent bio-ink for ocular surface regeneration by integrating Y-27632, a dual-media culture approach, and spheroid cell culture. Additionally, using auto-bioprinting technology, the limbal epithelial stem cell (LESC) spheroid bio-ink was precisely auto-bioprinted onto the curved surface of the corneal membrane, significantly accelerating corneal epithelial healing in an LSCD rabbit model.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 140-152"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973737","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":"Promotion of triple negative breast cancer immunotherapy by combining bioactive radicals with immune checkpoint blockade","authors":"Meixu Chen ,&nbsp;Linlin Song ,&nbsp;Yao Zhou ,&nbsp;Tianyue Xu ,&nbsp;Ting Sun ,&nbsp;Zhihui Liu ,&nbsp;Zihan Xu ,&nbsp;Yujie Zhao ,&nbsp;Peixin Du ,&nbsp;Yingying Ma ,&nbsp;Liwen Huang ,&nbsp;Xiaoting Chen ,&nbsp;Guang Yang ,&nbsp;Jing Jing ,&nbsp;Hubing Shi","doi":"10.1016/j.actbio.2025.01.015","DOIUrl":"10.1016/j.actbio.2025.01.015","url":null,"abstract":"<div><div>Although immunotherapy has revolutionized clinical cancer treatment, the efficacy is limited due to the lack of tumor-associated antigens (TAAs) and the presence of compensatory immune checkpoints. To overcome the deficiency, a nano-system loaded with ozone and CD47 inhibitor RRx-001 is designed and synthesized. Upon irradiation, reactive oxygen species (ROS) generated from ozone reacts with nitric oxide (NO) metabolized from RRx-001 to form reactive nitrogen species (RNS), which presents a much stronger cell-killing ability than ROS. Molecular mechanism studies further reveal that RNS induce extensive immunogenic cell death (ICD). The released TAAs promote infiltration of cytotoxic T lymphocytes, which provides the basis for immune checkpoint blockade (ICB) therapy. Meanwhile, RRx-001 carried by the nanoparticles and the produced radicals repolarize M2-type tumor-associated macrophages (TAMs) into the anti-tumor M1-type, consequently reversing the immunosuppressive tumor microenvironment (TME). In a xenograft triple-negative breast cancer (TNBC) animal model, O₃–001@lipo (liposome enwrapping O₃ and RRx-001) plus irradiation shows a significant anti-tumor efficacy by improving cytotoxic lymphocyte infiltration and regulating immunosuppressive TME. In summary, the O₃–001@lipo nano-system triggered by irradiation potently improves the efficacy of immunotherapy by introducing strong cytotoxic RNS, which not only enriches the toolbox of ICD inducer but also provides a strategy of treatment for immune deficient tumor.</div></div><div><h3>Statement of significance</h3><div>This study introduces a nano-system that leverages ozone and RRx-001 in the presence of X-ray irradiation to generate reactive nitrogen species, enhancing immunogenic cell death and promoting T-lymphocyte infiltration in triple-negative breast cancer, addressing a significant unmet need in the field.</div><div>The scientific contribution is the development of a clinically translatable nano-system that not only induces ICD but also reshapes the tumor microenvironment, which is expected to have a profound impact on the readership in pharmaceutics, material science, and nano-bio interaction, particularly for those interested in advanced immune therapy approaches.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 305-322"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980978","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":"SiO2-based inorganic nanofiber aerogel with rapid hemostasis and liver wound healing functions","authors":"Jimin Huang ,&nbsp;Yi Zheng ,&nbsp;Wenping Ma ,&nbsp;Yahui Han ,&nbsp;Jianmin Xue ,&nbsp;Zhiguang Huan ,&nbsp;Chengtie Wu ,&nbsp;Yufang Zhu","doi":"10.1016/j.actbio.2025.01.027","DOIUrl":"10.1016/j.actbio.2025.01.027","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Non-compressible hemostasis and promoting tissue healing are important in soft tissue trauma repair. Inorganic aerogels show superior performance in rapid hemostasis or promoting tissue healing, but simultaneously promoting non-compressive hemostasis and soft tissue healing still remains a challenge. Herein, SiO&lt;sub&gt;2&lt;/sub&gt;-based inorganic nanofiber aerogels (M&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt;, M=Ca, Mg, and Sr) were prepared by freeze-drying the mixture of bioactive silicates-deposited SiO&lt;sub&gt;2&lt;/sub&gt; nanofibers and SiO&lt;sub&gt;2&lt;/sub&gt; sol. These M&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogels have a three-dimensional highly-interconnected porous structure, remarkable flexibility, high absorption, good hydrophilicity, negative zeta potential, and bioactive ions releasing capacity. M&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogels not only exhibited satisfactory hemostasis activities &lt;em&gt;in vitro,&lt;/em&gt; but also possessed high hemostatic efficacy in compressible rabbit femoral artery injury bleeding model and non-compressible rat liver puncture bleeding model compared to medical gauze and gelatin sponge. M&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogel had low blood clotting index of &lt;em&gt;Ca&lt;/em&gt;. 10 % and short partial thromboplastin time of &lt;em&gt;ca&lt;/em&gt;. 82 s &lt;em&gt;in vitro&lt;/em&gt;, and could greatly short bleeding time by &gt;50 % and decrease blood loss by about 80 % compared to medical gauze and gelatin sponge in non-compressible hemostasis. Sr&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogel showed optimal bioactivities on promoting cell proliferation, cell migration, and the expression of liver function and angiogenesis related genes and proteins &lt;em&gt;in vitro&lt;/em&gt;. Importantly, Sr&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogel possessed a noteworthy function to promote liver soft tissue healing &lt;em&gt;in vivo&lt;/em&gt; by releasing bioactive ions and providing a highly-interconnected porous structure to support vascular development and tissue regeneration. Overall, Sr&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogel has great potential for integrated rapid hemostasis and soft tissue healing, which is promising in soft tissue trauma therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Non-compressible hemorrhage and soft tissue impairment are the main causes of mortality in emergency trauma. Inorganic aerogels with high porosity and outstanding flexibility can rapidly absorb blood to pro-coagulation and fill in irregular trauma without compression, but the low bioactivity limited the ability to promote soft tissue healing. Herein, SiO&lt;sub&gt;2&lt;/sub&gt;-based inorganic nanofiber aerogels (M&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt;, M=Ca, Mg, and Sr) were prepared by freeze-drying the mixture of bioactive silicates-deposited SiO&lt;sub&gt;2&lt;/sub&gt; nanofibers and SiO&lt;sub&gt;2&lt;/sub&gt; sol. M&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogels possessed high bioactivity and exhibited superior hemostatic performance in compressible and non-compressible bleeding model. Furthermore, Sr&lt;sup&gt;2+&lt;/sup&gt;@SiO&lt;sub&gt;2&lt;/sub&gt; aerogel showed optimal bioactivities on c","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 483-497"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017856","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 characterization of collagen architecture and mechanical properties of tissue engineered atherosclerotic plaque cap analogs","authors":"Hanneke Crielaard ,&nbsp;Tamar B. Wissing ,&nbsp;Su Guvenir Torun ,&nbsp;Gert-Jan Kremers ,&nbsp;Pablo de Miguel ,&nbsp;Ranmadusha M. Hengst ,&nbsp;Frank J.H. Gijsen ,&nbsp;Ali C. Akyildiz ,&nbsp;Kim van der Heiden","doi":"10.1016/j.actbio.2025.01.035","DOIUrl":"10.1016/j.actbio.2025.01.035","url":null,"abstract":"<div><div>Many cardiovascular events are triggered by fibrous cap rupture of an atherosclerotic plaque in arteries. However, cap rupture, including the impact of the cap's structural components, is poorly understood. To obtain better mechanistic insights in a biologically and mechanically controlled environment, we previously developed a tissue-engineered fibrous cap model. In the current study, we characterized the (local) structural and mechanical properties of these tissue-engineered cap analogs. Twenty-four collagenous cap analogs were cultured. The analogs were imaged with multiphoton microscopy with second-harmonic generation to obtain local collagen fiber orientation and dispersion. Then, the analogs were mechanically tested under uniaxial tensile loading until failure, and the local deformation (strain) and failure characteristics were analyzed. Our results demonstrated that the tissue-engineered analogs mimic the dominant (circumferential) fiber direction of human plaques. The analogs also exhibited a physiological strain stiffening response, similar to human fibrous plaque caps. Ruptures in the analogs initiated in and propagated towards local high-strain regions. The local strain values at the rupture sites were similar to the ones reported for carotid human fibrous plaque tissue. Finally, the study revealed that the rupture propagation path in the analogs followed the local fiber direction.</div></div><div><h3>Statement of significance</h3><div>Many cardiovascular events are triggered by mechanical rupture of atherosclerotic plaque caps. Yet, cap rupture mechanics is poorly understood. This is mainly due to the scarcity of plaques for high-throughput testing and the structural complexity of plaques. To overcome this, we previously developed tissue-engineered cap analogs. The current study characterizes (local) structural and mechanical properties of these cap analogs. Our findings show that: (1) cap analogs closely mimic human fibrous caps, including fiber orientation and strain stiffening responses; (2) structural and mechanical properties of cap analogs are associated, which provides critical information for understanding plaque rupture; and (3) cap ruptures commonly start in and propagate towards high-strain areas, indicating the potential use of strain measurements for cap rupture risk assessment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 185-193"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043863","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":"Quantification of 3D microstructures in Achilles tendons during in situ loading reveals anisotropic fiber response","authors":"Maria Pierantoni ,&nbsp;Kunal Sharma ,&nbsp;Joeri Kok ,&nbsp;Vladimir Novak ,&nbsp;Pernilla Eliasson ,&nbsp;Hanna Isaksson","doi":"10.1016/j.actbio.2025.01.023","DOIUrl":"10.1016/j.actbio.2025.01.023","url":null,"abstract":"<div><div>While the number of studies investigating Achilles tendon pathologies has grown exponentially, more research is needed to gain a better understanding of the complex relation between its hierarchical structure, mechanical response, and failure. At the microscale, collagen fibers are, with some degree of dispersion, primarily aligned along the principal loading direction. However, during tension, rearrangements and reorientations of these fibers are believed to occur. As 3D micro-movements are hard to capture, the precise nature of this fiber reorganization remains unknown. This study aimed to visualize and quantify the intricate fiber changes occurring within rat Achilles tendons under tension. Rat tendons were <em>in situ</em> loaded with concurrent synchrotron phase contrast microCT imaging. The results are heterogenous and show that collagen fibers’ response to loading is nonuniform and depends on anatomical orientation. Furthermore, damage propagation could be visualized, revealing that in the presence of heterotopic ossification, damage proceeds within the ossified deposits rather than at the interface between hard and soft tissues. Our approach could effectively capture the microstructural changes occurring during loading and shows promise in understanding the relation between microstructure and mechanical response for ex-vivo Achilles tendons and other biological tissues.</div></div><div><h3>Statement of Significance</h3><div>Achilles tendons endure high mechanical loads during daily motion and physical activities. Understanding the structural and mechanical responses of Achilles tendons to such loads is vital for elucidating their function in health and pathology. We have combined the use of synchrotron phase contrast microCT with <em>in situ</em> mechanical loading to contribute to a better understanding of the relation between microstructural response and organ scale mechanical properties. The proposed methodology will be valuable for future research into the interplay between structure, mechanics, and pathology of tendons, and for the development of more effective strategies to preserve tendon function and possibly mitigating musculoskeletal disorders.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 246-257"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973718","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 subtype specific probe for targeted magnetic resonance imaging of M2 tumor-associated macrophages in brain tumors","authors":"Yuancheng Li ,&nbsp;Anbu Mozhi Thamizhchelvan ,&nbsp;Hedi Ma ,&nbsp;Jonathan Padelford ,&nbsp;Zhaobin Zhang ,&nbsp;Tianhe Wu ,&nbsp;Quanquan Gu ,&nbsp;Zi Wang ,&nbsp;Hui Mao","doi":"10.1016/j.actbio.2025.01.003","DOIUrl":"10.1016/j.actbio.2025.01.003","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Pro-tumoral M2 tumor-associated macrophages (TAMs) play a critical role in the tumor immune microenvironment (TIME), making them an important therapeutic target for cancer treatment. Approaches for imaging and monitoring M2 TAMs, as well as tracking their changes in response to tumor progression or treatment are highly sought-after but remain underdeveloped. Here, we report an M2-targeted magnetic resonance imaging (MRI) probe based on sub-5 nm ultrafine iron oxide nanoparticles (uIONP), featuring an anti-biofouling coating to prevent non-specific macrophage uptake and an M2-specific peptide ligand (M2pep) for active targeting of M2 TAMs. The targeting specificity of M2pep-uIONP was validated &lt;em&gt;in vitro,&lt;/em&gt; using M0, M1, and M2 macrophages, and &lt;em&gt;in vivo,&lt;/em&gt; using an orthotopic patient-tissue-derived xenograft (PDX) mouse model of glioblastoma (GBM). MRI of the mice revealed hypointense contrast in T&lt;sub&gt;2&lt;/sub&gt;-weighted images of intracranial tumors 24 h after receiving intravenous (i.v.) injection of M2pep-uIONP. In contrast, no noticeable contrast change was observed in mice receiving scrambled-sequence M2pep-conjugated uIONP (scM2pep-uIONP) or the commercially available iron oxide nanoparticle formulation, Ferumoxytol. Measurement of nanoparticle-induced T&lt;sub&gt;2&lt;/sub&gt; value changes in tumors showed 38 %, 9 %, and 2 % decrease for M2pep-uIONP, scM2pep-uIONP, and Ferumoxytol, respectively. Moreover, M2pep-uIONP exhibited 88.7-fold higher intra-tumoral accumulation compared to co-injected Ferumoxytol at 24 h post-injection. Immunofluorescence-stained tumor sections showed that CD68&lt;sup&gt;+&lt;/sup&gt;/CD163&lt;sup&gt;+&lt;/sup&gt; M2 TAMs were highly co-localized with Cy7-M2pep-uIONP, but not with Cy7-scM2pep-uIONP and Cy7-Ferumoxytol. Flow cytometry analysis revealed 26 ± 10 % of M2 TAMs were targeted by M2pep-uIONP, which was significantly higher than Ferumoxytol (16 ± 1 %) and scM2pep-uIONP (13 ± 4 %) with the same dosage (20 mg Fe/kg). These findings demonstrate that M2pep-uIONP functions as a ligand-mediated MRI probe for targeted imaging of M2 TAMs in GBM, with potential applications for imaging of M2 TAM in other cancer types.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of Significance&lt;/h3&gt;&lt;div&gt;Targeting the pro-tumoral M2 subtype of tumor-associated macrophages (TAMs) to modulate the tumor immune microenvironment (TIME) is an emerging strategy for developing novel cancer therapies and enhancing the efficacy of existing treatments. In this study, we have developed a magnetic resonance imaging (MRI) probe using sub-5 nm ultrafine iron oxide nanoparticles (uIONP), which are coated with an anti-biofouling polymer and conjugated to an M2-specific peptide ligand (M2pep). Our results demonstrate that M2pep-uIONP exhibits an 88.7-fold higher accumulation in intracranial tumors in an orthotopic patient-derived xenograft (PDX) model of glioblastoma compared to the commercial iron oxide nanoparticle, Ferumoxytol. This enhanced accumulation enables M2pep-uIONP to i","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 336-351"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980975","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":"Wet adhesives for hard tissues","authors":"Sibei Tao ,&nbsp;Siying Tao ,&nbsp;Jiaojiao Yang ,&nbsp;Ping Fu ,&nbsp;Jianshu Li ,&nbsp;Jiyao Li","doi":"10.1016/j.actbio.2025.01.032","DOIUrl":"10.1016/j.actbio.2025.01.032","url":null,"abstract":"<div><div>The development of wet adhesives capable of bonding in aqueous environments, particularly for hard tissues such as bone, tooth, and cartilage, remains a significant challenge in material chemistry and biomedical research. Currently available hard tissue adhesives in clinical practice lack well-defined wet adhesion properties. Nature offers valuable inspiration through the adhesive mechanisms of marine organisms, advancing the design of bioinspired wet adhesives. Beyond biomimetic approaches, alternative strategies have emerged for the design of wet adhesives. This review systematically summarizes the current design strategies for wet adhesives, focusing on their applications to hard tissues. Then, the unique chemical, physical, mechanical, and biological requirements for wet adhesives applied to hard tissues are also discussed. The importance of understanding natural adhesion mechanisms and the need for high-performance materials that can meet the complex demands of hard tissue adhesion in a complex and delicate physiological microenvironment are highlighted. Finally, this review clarifies the future research directions that can further facilitate the clinical application of wet adhesives for hard tissues.</div></div><div><h3>Statement of significance</h3><div>The significance of this review lies in its comprehensive analysis of wet adhesives for hard tissues, a field that has been largely overlooked despite its critical importance in biomedical applications. The insights gained from studying natural adhesives and the translation of these mechanisms into synthetic materials have the potential to revolutionize medical procedures involving hard tissue repair and regeneration. This review meticulously addresses the distinct challenges and specific requirements of hard tissue adhesives, providing an exhaustive roadmap for researchers striving to develop wet adhesives that can endure the demanding physiological conditions inside the human body. In doing so, it aims to facilitate the transition from laboratory findings to practical clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 1-19"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043888","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":"Autophagy-targeted therapy for pulmonary inflammation by 2D MX2 (M = W, Nb; X = S, Se) nanosheets","authors":"Xiaofei Zhou ,&nbsp;Ning Zang ,&nbsp;Ting Yang ,&nbsp;Jimei Jia ,&nbsp;Hongyu Zhou ,&nbsp;Jianbo Jia","doi":"10.1016/j.actbio.2025.01.045","DOIUrl":"10.1016/j.actbio.2025.01.045","url":null,"abstract":"<div><div>For biomedical applications, two-dimensional transition metal dichalcogenides (2D TMDCs) are often combined with other elements or functionalized with specific surface ligands, while their intrinsic biological activities are not yet fully understood. This study investigates the anti-inflammatory potential of four unmodified 2D TMDCs, including WS₂, WSe₂, NbS₂, and NbSe₂ nanosheets, in LPS-activated MH-S cells <em>in vitro</em> and in a mouse model of pulmonary inflammation <em>in vivo</em>. Despite their varying compositions, these 2D TMDCs exhibited comparable anti-inflammatory effects in LPS-activated MH-S cells. Notably, the 2D TMDC nanosheets disrupted autophagic signaling pathways by adhering to the cell membrane and/or being internalized by the cells, thereby enhancing cellular autophagy and reducing the LPS-induced pro-inflammatory response by inhibiting NFκB phosphorylation. Their natural affinity for lung tissue makes these 2D TMDCs promising therapeutic agents for pulmonary inflammation, a finding further supported by results from the LPS-induced mouse model. Importantly, these results highlight the critical role of composition in the effects of 2D TMDCs on autophagic signaling, which could significantly advance the development of personalized therapies for pulmonary inflammation.</div></div><div><h3>Statement of significance</h3><div>Autophagy represents a promising target for therapeutic intervention in inflammatory lung diseases. This study explores various pristine two-dimensional transition metal dichalcogenides (2D TMDCs) as regulators of autophagy for targeted therapy in pulmonary inflammation. It emphasizes the crucial role of composition in shaping the effects of 2D TMDCs on autophagic signaling, thereby advancing the development of personalized therapies for pulmonary inflammation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"194 ","pages":"Pages 455-466"},"PeriodicalIF":9.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049068","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}