Acta Biomaterialia最新文献

{"title":"A biphasic drug-releasing microneedle with ROS scavenging and angiogenesis for the treatment of diabetic ulcers","authors":"Xinyue He ,&nbsp;Lianghong Peng ,&nbsp;Liming Zhou ,&nbsp;Huiling Liu ,&nbsp;Yifan Hao ,&nbsp;Yuhan Li ,&nbsp;Zijin lv ,&nbsp;Baohui Zeng ,&nbsp;Xinmin Guo ,&nbsp;Rui Guo","doi":"10.1016/j.actbio.2024.09.045","DOIUrl":"10.1016/j.actbio.2024.09.045","url":null,"abstract":"<div><div>Diabetic ulcers are one of the common complications in diabetic patients. Delayed wound healing is associated with persistent pro-inflammatory M1 polarization, reduced angiogenesis and increased reactive oxygen species (ROS) in the microenvironment. Wound healing consists of multiple phases and therefore requires treatment tailored to each phase. In this study, a biphasic drug-releasing microneedle (MN) was fabricated to achieve early ROS scavenging and late accelerated angiogenesis to promote wound healing. Vascular endothelial growth factor (VEGF) was first encapsulated in methacryloylated sulfonated chitosan (SCSMA) microspheres (V@MP), and then V@MP was loaded into hyaluronic acid (HA) microneedles along with cerium dioxide nanoparticles (CONPs). Rapid dissolution of HA rapidly releases the CONPs to clear ROS, whereas the V@MP stays in the wound. SCSMA slow degradation prolongs the release of VEGF, thereby promoting angiogenesis. <em>In vitro</em> and <em>in vivo</em> studies have shown that this biphasic drug-releasing smart microneedle improves cell proliferation and migration, effectively scavenges ROS, promotes angiogenesis and tissue regeneration, and synergistically promotes M2 macrophage polarization. It provides a new delivery mode for nano-enzymes and growth factors that could be multifunctional and synergistic in the treatment of diabetic ulcers.</div></div><div><h3>Statement of significance</h3><div>In our study, we present a microneedle (V@MP/C@MN) that can release drugs biphasically, which showed good repair ability in diabetic ulcer model. Large amounts of CONPs were rapidly released to alleviate oxidative stress during the inflammation of the wound, and V@MP stayed in the wound for a long period of time to release VEGF and promote angiogenesis in the late stage of wound healing. The results indicated that V@MP/C@MN could promote cell proliferation and migration, effectively scavenge ROS, promote angiogenesis and tissue regeneration, and synergistically promote M2 macrophage polarization, which could play a multifunctional and synergistic role in the treatment of diabetic ulcers.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 270-285"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373746","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":"Multi-functional nanosonosensitizer-engineered bacteria to overcome tumor hypoxia for enhanced sonodynamic therapy","authors":"Ting Wang ,&nbsp;Meng Du ,&nbsp;Zhen Yuan ,&nbsp;Jintong Guo ,&nbsp;Zhiyi Chen","doi":"10.1016/j.actbio.2024.10.013","DOIUrl":"10.1016/j.actbio.2024.10.013","url":null,"abstract":"<div><h3>Background</h3><div>Ultrasound-triggered sonodynamic therapy (SDT), with high safety and acceptance, has become a promising tumor treatment. However, the dense stroma, hypoxic microenvironment of tumor, and the unpredictable treatment timing limit the effectiveness of sonosensitizers and the antitumor therapeutic effect. Thus, it is crucial to develop an imaging-guided sensitization strategy for hypoxic tumor sonosensitization to improve the efficacy of SDT.</div></div><div><h3>Methods</h3><div>In this study, we developed a biohybrid system CB@HPP, which genetically engineered bacteria to express catalase (CB) and modified nanosonosensitizers (HPP) to the surface of these bacteria. Tumor hypoxia relief, tumor targeting, biocompatibility, and antitumor efficacy were evaluated through <em>in vitro</em> and <em>in vivo</em> experiments. In addition, the photoacoustic (PA), ultrasound (US), and fluorescence (FL) imaging effects of CB@HPP were evaluated <em>in vivo</em> and <em>in vitro</em>.</div></div><div><h3>Results</h3><div>After intravenous injection, CB@HPP was able to target tumor tissue. CB@HPP possessed efficient catalase activity and successfully degraded hydrogen peroxide to produce oxygen. Increased oxygen levels relief intratumoral hypoxia, thereby enhancing CB@HPP-mediated. In addition, CB@HPP showed FL/PA/US multimodal imaging capabilities, which reflects the aggregation effect of CB@HPP in the tumor and suggest the timing of treatment.</div></div><div><h3>Conclusion</h3><div>The biohybrid system CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.</div></div><div><h3>Statement of significance</h3><div>This study developed a sensitizing SDT strategy for imaging-guided drug-targeted delivery and <em>in situ</em> oxygen production. We designed a biohybrid system CB@HPP, which was hybridized by the engineered bacteria with catalytic oxygen production and nanosonosensitizer with multimodal imaging capability. CB@HPP significantly alleviates tumor hypoxia, and multimodal imaging-mediated oxygen-producing SDT effectively suppresses tumors. This integrated imaging and therapeutic biohybrid system provides a more efficient and attractive cancer treatment strategy for SDT.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 519-531"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482766","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":"Deciphering the complex mechanics of atherosclerotic plaques: A hybrid hierarchical theory-microrheology approach","authors":"Zhuo Chang ,&nbsp;Yidan Zhou ,&nbsp;Le Dong ,&nbsp;Lin-Ru Qiao ,&nbsp;Hui Yang ,&nbsp;Guang-Kui Xu","doi":"10.1016/j.actbio.2024.09.029","DOIUrl":"10.1016/j.actbio.2024.09.029","url":null,"abstract":"<div><div>Understanding the viscoelastic properties of atherosclerotic plaques at rupture-prone scales is crucial for assessing their vulnerability. Here, we develop a Hybrid Hierarchical theory-Microrheology (HHM) approach, enabling the analysis of multiscale mechanical variations and distribution changes in regional tissue viscoelasticity within plaques across different spatial scales. We disclose a universal two-stage power-law rheology in plaques, characterized by distinct power-law exponents (<em>α</em>_short and <em>α</em>_long), which serve as mechanical indexes for plaque components and assessing mechanical gradients. We further propose a self-similar hierarchical theory that effectively delineates plaque heterogeneity from the cytoplasm, cell, to tissue levels. Moreover, our proposed multi-layer perceptron model addresses the viscoelastic heterogeneity and gradients within plaques, offering a promising diagnostic strategy for identifying unstable plaques. These findings not only advance our understanding of plaque mechanics but also pave the way for innovative diagnostic approaches in cardiovascular disease management.</div></div><div><h3>Statement of significance</h3><div>Our study pioneers a Hybrid Hierarchical theory-Microrheology (HHM) approach to dissect the intricate viscoelasticity of atherosclerotic plaques, focusing on distinct components including cap fibrosis, lipid pools, and intimal fibrosis. We unveil a universal two-stage power-law rheology capturing mechanical variations across plaque structures. The proposed hierarchical model adeptly captures viscoelasticity changes from cytoplasm, cell to tissue levels. Based on the newly proposed markers, we further develop a machine learning (ML) diagnostic model that sets precise criteria for evaluating plaque components and heterogeneity. This work not only reveals the comprehensive mechanical heterogeneity within plaques but also introduces a mechanical marker-based ML strategy for assessing plaque conditions, offering a significant leap towards understanding and diagnosing atherosclerotic risks.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 399-412"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303128","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":"Ex vivo SIM-AFM measurements reveal the spatial correlation of stiffness and molecular distributions in 3D living tissue","authors":"Itsuki Shioka ,&nbsp;Ritsuko Morita ,&nbsp;Rei Yagasaki ,&nbsp;Duligengaowa Wuergezhen ,&nbsp;Tadahiro Yamashita ,&nbsp;Hironobu Fujiwara ,&nbsp;Satoru Okuda","doi":"10.1016/j.actbio.2024.09.023","DOIUrl":"10.1016/j.actbio.2024.09.023","url":null,"abstract":"<div><div>Living tissues each exhibit a distinct stiffness, which provides cells with key environmental cues that regulate their behaviors. Despite this significance, our understanding of the spatiotemporal dynamics and the biological roles of stiffness in three-dimensional tissues is currently limited due to a lack of appropriate measurement techniques. To address this issue, we propose a new method combining upright structured illumination microscopy (USIM) and atomic force microscopy (AFM) to obtain precisely coordinated stiffness maps and biomolecular fluorescence images of thick living tissue slices. Using mouse embryonic and adult skin as a representative tissue with mechanically heterogeneous structures inside, we validate the measurement principle of USIM-AFM. Live measurement of tissue stiffness distributions revealed the highly heterogeneous mechanical nature of skin, including nucleated/enucleated epithelium, mesenchyme, and hair follicle, as well as the role of collagens in maintaining its integrity. Furthermore, quantitative analysis comparing stiffness distributions in live tissue samples with those in preserved tissues, including formalin-fixed and cryopreserved tissue samples, unveiled the distinct impacts of preservation processes on tissue stiffness patterns. This series of experiments highlights the importance of live mechanical testing of tissue-scale samples to accurately capture the true spatiotemporal variations in mechanical properties. Our USIM-AFM technique provides a new methodology to reveal the dynamic nature of tissue stiffness and its correlation with biomolecular distributions in live tissues and thus could serve as a technical basis for exploring tissue-scale mechanobiology.</div></div><div><h3>Statement of significance</h3><div>Stiffness, a simple mechanical parameter, has drawn attention in understanding the mechanobiological principles underlying the homeostasis and pathology of living tissues. To explore tissue-scale mechanobiology, we propose a technique integrating an upright structured illumination microscope and an atomic force microscope. This technique enables live measurements of stiffness distribution and fluorescent observation of thick living tissue slices. Experiments revealed the highly heterogeneous mechanical nature of mouse embryonic and adult skin in three dimensions and the previously unnoticed influences of preservation techniques on the mechanical properties of tissue at microscopic resolution. This study provides a new technical platform for live stiffness measurement and biomolecular observation of tissue-scale samples with micron-scale resolution, thus contributing to future studies of tissue- and organ-scale mechanobiology.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 351-365"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395905","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":"Frederick J. Schoen, 2025 Acta Biomaterialia Gold Medal Award Recipient","authors":"","doi":"10.1016/j.actbio.2024.07.049","DOIUrl":"10.1016/j.actbio.2024.07.049","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Page 671"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657330","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":"Mixed-charge hyperbranched polymer nanoparticles with selective antibacterial action for fighting antimicrobial resistance","authors":"Yunyun Xue ,&nbsp;Chuyao Wang ,&nbsp;Yu Zhao ,&nbsp;Zihao Zhao ,&nbsp;Ronglu Cui ,&nbsp;Bin Du ,&nbsp;Lifeng Fang ,&nbsp;Jianyu Wang ,&nbsp;Baoku Zhu","doi":"10.1016/j.actbio.2024.08.044","DOIUrl":"10.1016/j.actbio.2024.08.044","url":null,"abstract":"<div><div>The escalating menace of antimicrobial resistance (AMR) presents a profound global threat to life and assets. However, the incapacity of metal ions/reactive oxygen species (ROS) or the indiscriminate intrinsic interaction of cationic groups to distinguish between bacteria and mammalian cells undermines the essential selectivity required in these nanomaterials for an ideal antimicrobial agent. Hence, we devised and synthesized a range of biocompatible mixed-charge hyperbranched polymer nanoparticles (MCHPNs) incorporating cationic, anionic, and neutral alkyl groups to effectively combat multidrug-resistant bacteria and mitigate AMR. This outcome stemmed from the structural, antibacterial activity, and biocompatibility analysis of seven MCHPNs, among which MCHPN7, with a ratio of cationic groups, anionic groups, and long alkyl chains at 27:59:14, emerged as the lead candidate. Importantly, owing to inherent differences in membrane potential among diverse species, alongside its nano-size (6–15 nm) and high hydrophilicity (<em>K_ow</em> = 0.04), MCHPN7 exhibited exceptional selective bactericidal effects over mammalian cells (selectivity index &gt; 564) in vitro and in vivo. By inducing physical membrane disruption, MCHPN7 effectively eradicated antibiotic-resistant bacteria and significantly delayed the emergence of bacterial resistance. Utilized as a coating, MCHPN7 endowed initially inert surfaces with the ability to impede biofilm formation and mitigate infection-related immune responses in mouse models. This research heralds the advent of biocompatible polymer nanoparticles and harbors significant implications in our ongoing combat against AMR.</div></div><div><h3>Statement of significance</h3><div>The escalating prevalence of antimicrobial resistance (AMR) has been acknowledged as one of the most significant threats to global health.</div><div>Therefore, a series of mixed-charge hyperbranched polymer nanoparticles (MCHPNs) with selective antibacterial action were designed and synthesized. Owing to inherent differences in membrane potential among diverse species and high hydrophilicity (<em>K_ow</em> = 0.04), the optimal nanoparticles exhibited exceptional selective bactericidal effects over mammalian cells (selectivity index &gt;564) and significantly delayed the emergence of bacterial resistance. Importantly, they endowed surfaces with the ability to impede biofilm formation and mitigate infection-related immune responses.</div><div>Furthermore, the above findings focus on addressing the problem of AMR in Post-Pandemic, which will for sure attract attention from both academic and industry research.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 545-558"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of migrasomes in immunity, barriers, and diseases","authors":"Changsheng Cai,&nbsp;Jun Shen","doi":"10.1016/j.actbio.2024.09.013","DOIUrl":"10.1016/j.actbio.2024.09.013","url":null,"abstract":"<div><div>Migrasomes are recently identified extracellular vesicles and organelles formed in conjunction with cell migration. They are situated at the rear of migrating cells, exhibit a circular or elliptical membrane-enclosed structure, and function as a new organelle. Migrasomes selectively sort intercellular components, mediating a cell migration-dependent release mechanism known as migracytosis and modulating cell–cell communication. Accumulated evidence clarifies migrasome formation processes and indicates their diverse functional roles. Migrasomes may also be potentially correlated with the occurrence, progression, and prognosis of certain diseases. Migrasomes’ involvement in physiological and pathological processes highlights their potential for expanding our understanding of biological procedures and as a target in clinical therapy. However, the precise mechanisms and full extent of their involvement in immunity, barriers, and diseases remain unclear. This review aimed to provide a comprehensive overview of the roles of migrasomes in human immunity and barriers, in addition to providing insights into their impact on human diseases.</div></div><div><h3>Statement of significance</h3><div>Migrasomes, newly identified extracellular vesicles and organelles, form during cell migration and are located at the rear of migrating cells. These circular or elliptical structures mediate migracytosis, selectively sorting intercellular components and modulating cell–cell communication. Evidence suggests diverse functional roles for migrasomes, including potential links to disease occurrence, progression, and prognosis. Their involvement in physiological and pathological processes highlights their significance in understanding biological procedures and potential clinical therapies. However, their exact mechanisms in immunity, barriers, and diseases remain unclear. This review provides an overview of migrasomes' roles in human immunity and barriers, and their impact on diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 88-102"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303141","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":"An injectable thermosensitive hydrogel delivering M2 macrophage-derived exosomes alleviates osteoarthritis by promoting synovial lymphangiogenesis","authors":"Xiongbo Song ,&nbsp;Jinwen Xiao ,&nbsp;Xiaojun Ai ,&nbsp;Yankun Li ,&nbsp;Li Sun ,&nbsp;Long Chen","doi":"10.1016/j.actbio.2024.09.034","DOIUrl":"10.1016/j.actbio.2024.09.034","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent chronic degenerative disease affecting millions worldwide, with current treatment measures lacking efficacy in slowing disease progression. The synovial lymphatic system (SLS) has emerged as a crucial player in OA pathogenesis, with compromised drainage function contributing to disease advancement. Lymphatic endothelial cells (LECs) within the SLS are influenced by synovial macrophages, whose precise impact on LEC function remains unclear. Exosomes released by macrophages may serve as mediators of this interaction, with potential implications for OA progression. Here, we propose that polarized macrophages modulate LEC activity via exosome release in synovial tissue, with M2 macrophage-derived exosomes (M2^Exo) promoting LEC proliferation, migration, and lymphangiogenesis, potentially offering a therapeutic avenue for OA. Moreover, we developed an injectable thermosensitive hydrogel with the characteristic of sustained release of M2^Exo for alleviating OA. The hydrogel was prepared by dynamically linking hyaluronic acid (HA) and Pluronic F-127 and loading M2^Exo, termed as M2^Exo loaded HP hydrogel. The <em>in vitro</em> and <em>in vivo</em> experiments showed that M2^Exo loaded HP hydrogel exhibits a controlled release profile of exosomes, thereby efficaciously fostering synovial lymphangiogenesis and enhancing synovial lymphatic drainage functionality under OA conditions, thus alleviating OA progression, and providing promising insights into OA therapeutic strategies.</div></div><div><h3>Statement of significance</h3><div>Osteoarthritis (OA) is a widespread degenerative disease with limited effective treatments to halt its progression. This research highlights the critical role of the synovial lymphatic system (SLS) in OA, focusing on how macrophage-derived exosomes influence lymphatic endothelial cell (LEC) function. We propose that M2 macrophage-derived exosomes (M2^Exo) enhance LEC activity, promoting lymphangiogenesis, and offering a therapeutic approach for OA. Furthermore, we developed an injectable thermosensitive hydrogel (M2^Exo loaded HP hydrogel) for sustained M2^Exo release. Our <em>in vitro</em> and <em>in vivo</em> experiments demonstrate that this hydrogel supports synovial lymphangiogenesis and improves lymphatic drainage, effectively alleviating OA progression. This study presents significant advancements in OA therapy, offering new insights into its management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 130-142"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334134","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":"Multiscale fiber remodeling in the infarcted left ventricle using a stress-based reorientation law","authors":"Mohammad Mehri ,&nbsp;Hossein Sharifi ,&nbsp;Charles K. Mann ,&nbsp;Alexus L. Rockward ,&nbsp;Kenneth S. Campbell ,&nbsp;Lik Chuan Lee ,&nbsp;Jonathan F. Wenk","doi":"10.1016/j.actbio.2024.09.049","DOIUrl":"10.1016/j.actbio.2024.09.049","url":null,"abstract":"<div><div>The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI), this organization can become disrupted, leading to degraded pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and active), both myofibers and collagen fibers are reoriented. Simulations are conducted to predict the baseline fiber configuration in a normal LV as well as the adverse fiber reorientation that occurs due to different size MIs. The baseline model successfully captures the transmural variation of helical fiber angles within the LV wall, as well as the transverse fiber angle variation from base to apex. In the models of MI, the patterns of fiber reorientation in the infarct, border zone, and remote regions closely align with previous experimental findings, with a significant increase in fibers oriented in a left-handed helical configuration and increased dispersion in the infarct region. Furthermore, the severity of fiber reorientation and impairment of pumping performance both showed a correlation with the size of the infarct. The proposed multiscale modeling framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future.</div></div><div><h3>Statement of Significance</h3><div>The organization of muscle and collagen fibers within the heart plays a significant role in defining cardiac function. This organization can become disrupted after a heart attack, leading to degraded pumping performance. In the current study, we implemented a stress-based fiber reorientation law into a computer model of the heart, which seeks to realign the fibers such that contractile force and load bearing capabilities are maximized. The primary goal was to evaluate the effects of different sized heart attacks. We observed substantial fiber remodeling in the heart, which matched experimental observations. The proposed computational framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 337-350"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373680","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":"A bi-component model to assess the rheology of soft cellular aggregates probed using the micropipette aspiration technique","authors":"Giuseppe Sciumè ,&nbsp;Karine Guevorkian ,&nbsp;Pierre Nassoy","doi":"10.1016/j.actbio.2024.09.043","DOIUrl":"10.1016/j.actbio.2024.09.043","url":null,"abstract":"<div><div>The micro-pipette aspiration technique is a classical experiment used to characterize the physical properties of inert fluids and biological soft materials such as cellular aggregates. The physical parameters of the fluid, as viscosity and interfacial tension, are obtained by studying how the fluid enters the pipette when the suction pressure is increased and how it relaxes when the suction pressure is put to zero. A mathematical model representative of the experiment is needed to extrapolate the physical parameters of the fluid-like matter; however, for biological materials as cells or cell aggregates mathematical models are always based on strong starting hypotheses that impact the significance of the identified parameters. In this article, starting from the bi-constituent nature of the cell aggregate, we derive a general mathematical model based of a Cahn–Hilliard–Navier–Stokes set of equations. The model is applied to describe quantitatively the aspiration-retraction dynamics of a cell-aggregate into and out of a pipette. We demonstrate the predictive capability of the model and highlight the impact of the assumptions made on the identified parameters by studying two cases: one with a non-wetting condition between the cells and the wall of the pipette (classical assumption in the literature) and the second one, which is more realistic, with a partial wetting condition (contact angle <em>θ_s</em> = 150°). Furthermore, our results provide a purely physical explanation to the asymmetry between the aspiration and retraction responses which is alternative to the proposed hypothesis of an mechano-responsive alteration of the surface tension of the cell aggregate.</div></div><div><h3>Statement of significance</h3><div>Our study introduces a general mathematical model, based on the Cahn-Hilliard-Navier-Stokes equations, tailored to model micro-pipette aspiration of cell aggregates. The model accounts for the multi-component structure of the cell aggregate and its intrinsic viscoelastic rheology. By challenging prevailing assumptions, particularly regarding perfect non-wetting conditions and the mechano-responsive alteration of cell surface tension, we demonstrate the reliability of the mathematical model and elucidate the mechanisms at play, offering a purely physical explanation for observed asymmetries between the aspiration and retraction stages of the experiment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"189 ","pages":"Pages 449-460"},"PeriodicalIF":9.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373745","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}