Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.11.040
Derek Avery , Lais Morandini , Luke Sheakley , Asmaa Alajmi , Leah Bergey , Henry J. Donahue , Rebecca K. Martin , Rene Olivares-Navarrete
Obesity is a metabolic disease resulting from excess body fat accumulation associated with chronic systemic inflammation. Obesity has been shown to impact the function and activity of neutrophils, macrophages, and T cells, contributing to higher circulating levels of pro-inflammatory cytokines. Biomaterial surface properties such as roughness and hydrophilicity can influence the behavior of immune cells in the peri-implant microenvironment. This study aimed to determine how obesity induced by a high-fat diet (HFD) affects the inflammatory response to modified titanium (Ti) implants and subsequent bone formation. Obese mice had significantly more neutrophils, pro-inflammatory macrophages, and T cells and fewer anti-inflammatory macrophages and mesenchymal stem cells (MSCs) in the peri-implant tissue than lean mice. Obesity also increased circulating adipokines and pro-inflammatory cytokines when compared to lean animals. Bone formation around Ti implants was reduced in obese mice compared to controls. Adoptive transfer of bone marrow cells isolated from obese mice into wild-type mice demonstrated the localized impact of obesity on immune cell function and phenotype, promoting a pro-inflammatory peri-implant microenvironment and attenuating bone formation post-implantation. These results show that obesity significantly affects the inflammatory response to modified Ti implants, prolonging the pro-inflammatory response to the implanted biomaterial and compromising bone formation.
Statement of significance
Obesity has been shown to significantly alter physiological processes, including the behavior of immune cells, inducing a state of systemic chronic inflammation. Our study demonstrates that obesity-induced via a high-fat diet alters immune cell response to implanted biomaterials, with increased pro-inflammatory response and attenuated immunomodulation that results in decreased biomaterial integration.
肥胖症是一种代谢性疾病,是由于体内脂肪堆积过多并伴有慢性全身性炎症所致。研究表明,肥胖会影响中性粒细胞、巨噬细胞和 T 细胞的功能和活性,导致循环中促炎细胞因子水平升高。粗糙度和亲水性等生物材料表面特性会影响种植体周围微环境中免疫细胞的行为。本研究旨在确定高脂饮食(HFD)诱导的肥胖如何影响对改良钛(Ti)植入物的炎症反应以及随后的骨形成。与瘦小鼠相比,肥胖小鼠种植体周围组织中的中性粒细胞、促炎巨噬细胞和T细胞明显增多,而抗炎巨噬细胞和间充质干细胞(MSCs)则较少。与瘦小动物相比,肥胖还增加了循环脂肪因子和促炎细胞因子。与对照组相比,肥胖小鼠 Ti 植入体周围的骨形成减少。将从肥胖小鼠体内分离出的骨髓细胞收养转移到野生型小鼠体内,证明了肥胖对免疫细胞功能和表型的局部影响,促进了种植体周围的促炎微环境,并削弱了种植后的骨形成。这些结果表明,肥胖会严重影响改良 Ti 植入物的炎症反应,延长植入生物材料的促炎症反应,影响骨形成。意义说明:肥胖已被证明会显著改变生理过程,包括免疫细胞的行为,诱发全身慢性炎症。我们的研究表明,通过高脂饮食引起的肥胖会改变免疫细胞对植入生物材料的反应,促炎反应增加和免疫调节减弱会导致生物材料整合能力下降。
{"title":"Obesity prolongs the pro-inflammatory response and attenuates bone healing on titanium implants","authors":"Derek Avery , Lais Morandini , Luke Sheakley , Asmaa Alajmi , Leah Bergey , Henry J. Donahue , Rebecca K. Martin , Rene Olivares-Navarrete","doi":"10.1016/j.actbio.2024.11.040","DOIUrl":"10.1016/j.actbio.2024.11.040","url":null,"abstract":"<div><div>Obesity is a metabolic disease resulting from excess body fat accumulation associated with chronic systemic inflammation. Obesity has been shown to impact the function and activity of neutrophils, macrophages, and T cells, contributing to higher circulating levels of pro-inflammatory cytokines. Biomaterial surface properties such as roughness and hydrophilicity can influence the behavior of immune cells in the peri-implant microenvironment. This study aimed to determine how obesity induced by a high-fat diet (HFD) affects the inflammatory response to modified titanium (Ti) implants and subsequent bone formation. Obese mice had significantly more neutrophils, pro-inflammatory macrophages, and T cells and fewer anti-inflammatory macrophages and mesenchymal stem cells (MSCs) in the peri-implant tissue than lean mice. Obesity also increased circulating adipokines and pro-inflammatory cytokines when compared to lean animals. Bone formation around Ti implants was reduced in obese mice compared to controls. Adoptive transfer of bone marrow cells isolated from obese mice into wild-type mice demonstrated the localized impact of obesity on immune cell function and phenotype, promoting a pro-inflammatory peri-implant microenvironment and attenuating bone formation post-implantation. These results show that obesity significantly affects the inflammatory response to modified Ti implants, prolonging the pro-inflammatory response to the implanted biomaterial and compromising bone formation.</div></div><div><h3>Statement of significance</h3><div>Obesity has been shown to significantly alter physiological processes, including the behavior of immune cells, inducing a state of systemic chronic inflammation. Our study demonstrates that obesity-induced via a high-fat diet alters immune cell response to implanted biomaterials, with increased pro-inflammatory response and attenuated immunomodulation that results in decreased biomaterial integration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 473-486"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717780","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.10.048
Jude Cameron , Tiziana Di Luccio , Jordan Barr , Lison Rocher , Eugene Kim , Gary H. Menary , Alex B. Lennon , Julia A. Kornfield
Crystal structure and morphology dictate the mechanical, thermal, and degradation properties of poly l-lactide (PLLA), the structural polymer of the first clinically approved bioresorbable vascular scaffolds (BVS). New experimental methods are developed to reveal the underlying mechanisms governing structure formation during the crimping step of the BVS manufacturing process. Our research specifically examines the “U-bends” – the region where the curvature is highest and stress is maximised during crimping, which can potentially lead to failure of the device with dramatic consequences on patient life. A custom-made crimping rig operated at a synchrotron beamline enabled collection of wide- and small-angle X-ray scattering (WAXS/SAXS) to probe local variations of the polymer morphology as a function of position in the crest of multiple U-bends with 5 μm resolution in situ after crimping and expansion. Additionally, polarised light microscopy (PLM) images of these deformed U-bends revealed areas with varying stress distribution developed during crimping and expansion. These variations were dependant on the initial biaxial stretching processing step. The integrated X-ray scattering-microscopy approach offered a comprehensive work-flow for uncovering the intricate relationship between processing conditions and the corresponding spatially-resolved semicrystalline morphology of a BVS.
Statement of Significance
This research introduces a new method for gaining critical insights into the structural changes that occur during the manufacturing process of bioresorbable vascular scaffolds (BVS). The crimping and expansion of poly l-lactide (PLLA) – the structural material of BVS – are sequential manufacturing steps characterised by highly non-linear deformations at temperature conditions that remain unexplored.
By utilising synchrotron X-ray scattering techniques alongside polarised light microscopy, we have developed new experimental methods to uncover the mechanisms governing structure formation during processing. This innovative approach not only deepens our understanding of the relationship between processing conditions and polymer morphology but also establishes the foundation for real-time observation methods during crimping and expansion. By improving the design and performance of BVS, this study has the potential to advance cardiovascular treatments and improve patient safety, making it highly relevant and impactful to both scientific research and clinical applications.
晶体结构和形态决定了聚 l-内酰胺(PLLA)的机械、热和降解特性,聚 l-内酰胺是第一种经临床批准的生物可吸收血管支架(BVS)的结构聚合物。我们开发了新的实验方法来揭示 BVS 制造过程中卷曲步骤中结构形成的基本机制。我们的研究特别考察了 "U 形弯曲"--弯曲度最高的区域,也是卷曲过程中应力最大的区域,这有可能导致装置失效,对患者的生命造成严重影响。在同步辐射光束线运行的定制卷曲设备可收集广角和小角 X 射线散射(WAXS/SAXS),以 5 μm 的分辨率在卷曲和膨胀后的原位探测多个 U 形弯曲波峰中聚合物形态的局部变化。此外,这些变形 U 形弯曲的偏振光显微镜(PLM)图像显示了在压接和膨胀过程中形成的不同应力分布区域。这些变化取决于最初的双轴拉伸加工步骤。综合 X 射线散射显微镜方法提供了一个全面的工作流程,用于揭示加工条件与 BVS 的相应空间分辨半晶体形态之间的复杂关系。意义说明:这项研究引入了一种新方法,用于深入了解生物可吸收血管支架(BVS)制造过程中发生的结构变化。生物可吸收血管支架的结构材料--聚乳酸(PLLA)的卷曲和膨胀是连续的制造步骤,其特点是在温度条件下发生高度非线性形变,而这一点尚未得到研究。通过利用同步辐射 X 射线散射技术和偏振光显微镜,我们开发出了新的实验方法来揭示加工过程中结构形成的机理。这种创新方法不仅加深了我们对加工条件与聚合物形态之间关系的理解,还为卷曲和膨胀过程中的实时观测方法奠定了基础。通过改进 BVS 的设计和性能,这项研究有可能推动心血管治疗的发展并提高患者的安全性,因此对科学研究和临床应用都具有重大意义和影响。
{"title":"Employing synchrotron X-ray scattering and microscopy to explore microstructural mysteries in bioresorbable vascular scaffolds","authors":"Jude Cameron , Tiziana Di Luccio , Jordan Barr , Lison Rocher , Eugene Kim , Gary H. Menary , Alex B. Lennon , Julia A. Kornfield","doi":"10.1016/j.actbio.2024.10.048","DOIUrl":"10.1016/j.actbio.2024.10.048","url":null,"abstract":"<div><div>Crystal structure and morphology dictate the mechanical, thermal, and degradation properties of poly l-lactide (PLLA), the structural polymer of the first clinically approved bioresorbable vascular scaffolds (BVS). New experimental methods are developed to reveal the underlying mechanisms governing structure formation during the crimping step of the BVS manufacturing process. Our research specifically examines the “U-bends” – the region where the curvature is highest and stress is maximised during crimping, which can potentially lead to failure of the device with dramatic consequences on patient life. A custom-made crimping rig operated at a synchrotron beamline enabled collection of wide- and small-angle X-ray scattering (WAXS/SAXS) to probe local variations of the polymer morphology as a function of position in the crest of multiple U-bends with 5 μm resolution <em>in situ</em> after crimping and expansion. Additionally, polarised light microscopy (PLM) images of these deformed U-bends revealed areas with varying stress distribution developed during crimping and expansion. These variations were dependant on the initial biaxial stretching processing step. The integrated X-ray scattering-microscopy approach offered a comprehensive work-flow for uncovering the intricate relationship between processing conditions and the corresponding spatially-resolved semicrystalline morphology of a BVS.</div></div><div><h3>Statement of Significance</h3><div>This research introduces a new method for gaining critical insights into the structural changes that occur during the manufacturing process of bioresorbable vascular scaffolds (BVS). The crimping and expansion of poly l-lactide (PLLA) – the structural material of BVS – are sequential manufacturing steps characterised by highly non-linear deformations at temperature conditions that remain unexplored.</div><div>By utilising synchrotron X-ray scattering techniques alongside polarised light microscopy, we have developed new experimental methods to uncover the mechanisms governing structure formation during processing. This innovative approach not only deepens our understanding of the relationship between processing conditions and polymer morphology but also establishes the foundation for real-time observation methods during crimping and expansion. By improving the design and performance of BVS, this study has the potential to advance cardiovascular treatments and improve patient safety, making it highly relevant and impactful to both scientific research and clinical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 175-188"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678015","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}
Posterior capsule opacification (PCO) is the most common complication after cataract surgery. It is primarily caused by the proliferation, migration, and adhesion of residual lens epithelial cells within the capsular bag following phacoemulsification and intraocular lens (IOL) implantation. Although investigations of surface modification onto IOL have partially reduced PCO development in recent years, there are still challenges in long-term efficacy and intraocular biocompatibility. In this study, a cascade catalytic system is constructed using natural enzymes onto mesoporous silica nanoparticles (MSNs), which are subsequently fixed to the surface of IOL through layer-by-layer self-assemble of alternating positive and negative charges. The cascade catalytic reaction is trigged simply by glucose within the pouch to produce reactive oxygen species (ROS) without introducing any toxic drugs or external energy, attempting to minimize the possible toxic side effects to surrounding tissues. In vivo and in vitro experiments indicate the effective inhibition of PCO and favorable intraocular compatibility of the cascade catalytic platform modified IOL. More importantly, the modified IOL retains good optical performance and imaging quality, demonstrating promising prospects for application. This study provides a new possibility for enhanced and safer PCO prevention, playing great significance in clinical treatment.
Statement of Significance
Cascade catalytic nanoparticles-loaded multilayer modified IOL is obtained via LbL technique.
The multilayer coating improves both the loading capacity and the activity of the cascade catalytic nanoparticles.
The cascade catalytic reaction is trigged by glucose, producing ROS that efficiently induces apoptosis and death of remaining cells on IOL without introducing any toxic drugs or external energy.
The innovative IOL provides a promising approach for enhanced and safer prevention of PCO.
{"title":"Cascade catalytic multilayer modified intraocular lens for enhanced and safer posterior capsule opacification prevention","authors":"Qingqing Jia, Youfei Wei, Yulin Hu, Yuexin Yang, Wenxin Hong, Huiying Huang, Quankui Lin","doi":"10.1016/j.actbio.2024.12.016","DOIUrl":"10.1016/j.actbio.2024.12.016","url":null,"abstract":"<div><div>Posterior capsule opacification (PCO) is the most common complication after cataract surgery. It is primarily caused by the proliferation, migration, and adhesion of residual lens epithelial cells within the capsular bag following phacoemulsification and intraocular lens (IOL) implantation. Although investigations of surface modification onto IOL have partially reduced PCO development in recent years, there are still challenges in long-term efficacy and intraocular biocompatibility. In this study, a cascade catalytic system is constructed using natural enzymes onto mesoporous silica nanoparticles (MSNs), which are subsequently fixed to the surface of IOL through layer-by-layer self-assemble of alternating positive and negative charges. The cascade catalytic reaction is trigged simply by glucose within the pouch to produce reactive oxygen species (ROS) without introducing any toxic drugs or external energy, attempting to minimize the possible toxic side effects to surrounding tissues. In vivo and in vitro experiments indicate the effective inhibition of PCO and favorable intraocular compatibility of the cascade catalytic platform modified IOL. More importantly, the modified IOL retains good optical performance and imaging quality, demonstrating promising prospects for application. This study provides a new possibility for enhanced and safer PCO prevention, playing great significance in clinical treatment.</div></div><div><h3>Statement of Significance</h3><div>Cascade catalytic nanoparticles-loaded multilayer modified IOL is obtained via LbL technique.</div><div>The multilayer coating improves both the loading capacity and the activity of the cascade catalytic nanoparticles.</div><div>The cascade catalytic reaction is trigged by glucose, producing ROS that efficiently induces apoptosis and death of remaining cells on IOL without introducing any toxic drugs or external energy.</div><div>The innovative IOL provides a promising approach for enhanced and safer prevention of PCO.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 248-259"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792948","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.12.006
Yufei Wu , Vega Lloveras , Silvia Lope-Piedrafita , Marta Mulero-Acevedo , Ana Paula Candiota , José Vidal-Gancedo
This study introduces a series of water-soluble radical dendrimers (G0 to G5) as promising magnetic resonance imaging (MRI) contrast agents that could potentially address clinical safety concerns associated with current gadolinium-based contrast agents. By using a simplified synthetic approach based on a cyclotriphosphazene core and lysine-derived branching units, we successfully developed a G5 dendrimer containing up to 192 units of 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO) radical. This synthesis offers advantages including ease of preparation, purification, and tunable water solubility through the incorporation of glutamic acid anion residues. Comprehensive characterization using 1H NMR, FT-IR, and SEC-HPLC confirmed the dendrimers' structures and purity. Electron paramagnetic resonance (EPR) spectroscopy revealed that TEMPO groups in higher generation dendrimers exhibited decreased mobility and stronger spin exchange in their local environments. In vitro MRI showed that relaxivity (r1) increased with higher dendrimer generations, with G5 exhibiting an exceptionally high r1 of over 24 mM-1s-1. Molecular dynamics simulations provided crucial insights into structure-property relationships, revealing the importance of water accessibility to TEMPO groups for enhancing relaxivity. Vero cell viability assay demonstrated G3 and G3.5 have good biocompatibility. In vivo MRI experiments in mice demonstrated that G3.5 was excreted through the kidneys and selectively accumulated in glioblastoma tumors.
Statement of significance
This study explores a class of MRI contrast agents based on organic radical dendrimers as a potential alternative to gadolinium-based agents. We present a simplified synthesis method for water-soluble dendrimers containing up to 192 TEMPO radical units—the highest number achieved to date for this class of compounds—resulting in record-high relaxivity values. Our approach offers easier preparation, purification, and tunable water solubility, representing an improvement over existing methods. Through combined experimental and computational studies, we provide insights into the structure-property relationships governing relaxivity. In vivo experiments demonstrate the dendrimers' potential for glioblastoma imaging, with predominantly renal excretion. This work represents a step towards developing metal-free MRI contrast agents with promising relaxivity and biocompatibility, potentially opening new avenues for diagnostic imaging research.
{"title":"Synthesis and Relaxivity study of amino acid-branched radical dendrimers as MRI contrast agents for potential brain tumor imaging","authors":"Yufei Wu , Vega Lloveras , Silvia Lope-Piedrafita , Marta Mulero-Acevedo , Ana Paula Candiota , José Vidal-Gancedo","doi":"10.1016/j.actbio.2024.12.006","DOIUrl":"10.1016/j.actbio.2024.12.006","url":null,"abstract":"<div><div>This study introduces a series of water-soluble radical dendrimers (G0 to G5) as promising magnetic resonance imaging (MRI) contrast agents that could potentially address clinical safety concerns associated with current gadolinium-based contrast agents. By using a simplified synthetic approach based on a cyclotriphosphazene core and lysine-derived branching units, we successfully developed a G5 dendrimer containing up to 192 units of 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO) radical. This synthesis offers advantages including ease of preparation, purification, and tunable water solubility through the incorporation of glutamic acid anion residues. Comprehensive characterization using <sup>1</sup>H NMR, FT-IR, and SEC-HPLC confirmed the dendrimers' structures and purity. Electron paramagnetic resonance (EPR) spectroscopy revealed that TEMPO groups in higher generation dendrimers exhibited decreased mobility and stronger spin exchange in their local environments. <em>In vitro</em> MRI showed that relaxivity (<em>r</em><sub>1</sub>) increased with higher dendrimer generations, with G5 exhibiting an exceptionally high <em>r</em><sub>1</sub> of over 24 mM<sup>-1</sup>s<sup>-1</sup>. Molecular dynamics simulations provided crucial insights into structure-property relationships, revealing the importance of water accessibility to TEMPO groups for enhancing relaxivity. Vero cell viability assay demonstrated G3 and G3.5 have good biocompatibility. <em>In vivo</em> MRI experiments in mice demonstrated that G3.5 was excreted through the kidneys and selectively accumulated in glioblastoma tumors.</div></div><div><h3>Statement of significance</h3><div>This study explores a class of MRI contrast agents based on organic radical dendrimers as a potential alternative to gadolinium-based agents. We present a simplified synthesis method for water-soluble dendrimers containing up to 192 TEMPO radical units—the highest number achieved to date for this class of compounds—resulting in record-high relaxivity values. Our approach offers easier preparation, purification, and tunable water solubility, representing an improvement over existing methods. Through combined experimental and computational studies, we provide insights into the structure-property relationships governing relaxivity. <em>In vivo</em> experiments demonstrate the dendrimers' potential for glioblastoma imaging, with predominantly renal excretion. This work represents a step towards developing metal-free MRI contrast agents with promising relaxivity and biocompatibility, potentially opening new avenues for diagnostic imaging research.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 461-472"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796682","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.12.012
E Du , Hongyuan Xu , Liliana Ponkratova
The intrinsic electrical and mechanical properties of cells are not only valuable biophysical markers reflective of physiological conditions but also play important roles in the development and progression of human diseases. Existing single-cell techniques are restricted to assessing either mechanical or electrical properties. We introduce the development of electro-deformation spectroscopy (EDS), namely the frequency-dependent electro-deformation, as a new method for simultaneous electrical and mechanical characterization of individual cells in suspension. To facilitate the practical use of this technology, we developed a testing procedure that evaluates red blood cells (RBCs) directly from whole blood in a simple microfluidic system, employing an electric field magnitude of 34 kV/m over a frequency range of 15 MHz to 100 kHz. The EDS measurement is performed under stationary conditions without special cell stabilization, at a moderate throughput of 50–100 cells per minute. We develop an experimental-computational framework to decouple cell electromechanics by optimizing the most suitable parameters of the relative permittivity of cell membrane, cytoplasm electrical conductivity, and membrane shear modulus. This technique, tested on RBCs from 4 healthy human samples, revealed membrane relative permittivity of 3.6 – 5.8, membrane shear modulus of 2.2 – 2.8 µN/m, and cytoplasm conductivity of 0.47 – 0.81 S/m. EDS analysis identifies the marked intrasample heterogeneity and individual variability in both cellular electrical and mechanical properties. The EDS framework can be readily used to test RBCs across different species, pathological states, and other cell types of similar structures as RBCs.
Statement of significance
This work introduces electro-deformation spectroscopy (EDS) as a unified method for simultaneous electrical and mechanical characterization of single cells in suspension. This is the first-of-its-kind technology for such purposes. EDS can be performed in a simple microfluidic system with minimal sample preparation, making it a convenient and powerful tool for label-free, non-invasive single-cell analysis. We validate the applicability of EDS by measuring the intrasample heterogeneity and individual variability based on the electromechanical parameters of interest for human red blood cells. Single-cell EDS has the potential to enable rapid and reliable detection of cellular changes by diseases or drug treatments and provide insights into the fundamental bioelectromechanical mechanisms of cellular adaptation and dysfunction. This work advances the field of single-cell analysis and contributes to the development of biomaterials and biotechnologies based on cellular electromechanics.
{"title":"Electro-deformation spectroscopy: A unified method for simultaneous electrical and mechanical characterization of single cells","authors":"E Du , Hongyuan Xu , Liliana Ponkratova","doi":"10.1016/j.actbio.2024.12.012","DOIUrl":"10.1016/j.actbio.2024.12.012","url":null,"abstract":"<div><div>The intrinsic electrical and mechanical properties of cells are not only valuable biophysical markers reflective of physiological conditions but also play important roles in the development and progression of human diseases. Existing single-cell techniques are restricted to assessing either mechanical or electrical properties. We introduce the development of electro-deformation spectroscopy (EDS), namely the frequency-dependent electro-deformation, as a new method for simultaneous electrical and mechanical characterization of individual cells in suspension. To facilitate the practical use of this technology, we developed a testing procedure that evaluates red blood cells (RBCs) directly from whole blood in a simple microfluidic system, employing an electric field magnitude of 34 kV/m over a frequency range of 15 MHz to 100 kHz. The EDS measurement is performed under stationary conditions without special cell stabilization, at a moderate throughput of 50–100 cells per minute. We develop an experimental-computational framework to decouple cell electromechanics by optimizing the most suitable parameters of the relative permittivity of cell membrane, cytoplasm electrical conductivity, and membrane shear modulus. This technique, tested on RBCs from 4 healthy human samples, revealed membrane relative permittivity of 3.6 – 5.8, membrane shear modulus of 2.2 – 2.8 µN/m, and cytoplasm conductivity of 0.47 – 0.81 S/m. EDS analysis identifies the marked intrasample heterogeneity and individual variability in both cellular electrical and mechanical properties. The EDS framework can be readily used to test RBCs across different species, pathological states, and other cell types of similar structures as RBCs.</div></div><div><h3>Statement of significance</h3><div>This work introduces electro-deformation spectroscopy (EDS) as a unified method for simultaneous electrical and mechanical characterization of single cells in suspension. This is the first-of-its-kind technology for such purposes. EDS can be performed in a simple microfluidic system with minimal sample preparation, making it a convenient and powerful tool for label-free, non-invasive single-cell analysis. We validate the applicability of EDS by measuring the intrasample heterogeneity and individual variability based on the electromechanical parameters of interest for human red blood cells. Single-cell EDS has the potential to enable rapid and reliable detection of cellular changes by diseases or drug treatments and provide insights into the fundamental bioelectromechanical mechanisms of cellular adaptation and dysfunction. This work advances the field of single-cell analysis and contributes to the development of biomaterials and biotechnologies based on cellular electromechanics.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 119-127"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792951","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.12.015
Liang Song , Zihe Zhai , Wei Ouyang , Jie Ding , Shuqin Wang , Shifen Li , Min Liang , Feng Xu , Changyou Gao
Hydrogel microparticles (HMPs) have many advantages for biomedical applications, particularly for minimally invasive therapy, for example, acute lung injury (ALI) that is characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators in the microenvironment. In this study, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were designed and prepared by using a membrane emulsification device. The HMPs were composed of double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal linkages and unsaturated double bonds. Surface-coating of inflammatory macrophage (M1) cell membranes was performed to obtain the membrane-coated HBPAK HMPs (mem HMPs) via electrostatic force. The mem HMPs exhibited strong ROS-scavenging and anti-inflammatory properties both in vitro and in vivo. After administered by inhalation in an ALI mouse model, the mem HMPs reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation. Our results suggest that the mem HMPs could serve as a potential therapeutic platform for treating inflammatory diseases with high efficiency.
Statement of significance
Hydrogel microparticles (HMPs) with minimally invasive delivery are advantageous for acute lung injury (ALI) characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators. Herein, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were prepared by copolymerizing double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal bonds and unsaturated double bonds in a membrane emulsification device. The HMPs covered with inflammatory macrophage (M1) cell membranes (mem HMPs) exhibited strong ROS-scavenging and anti-inflammation properties, reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation.
{"title":"Inhalation of macrophage membrane-coated hydrogel microparticles for inflammation alleviation of acute lung injury in vivo","authors":"Liang Song , Zihe Zhai , Wei Ouyang , Jie Ding , Shuqin Wang , Shifen Li , Min Liang , Feng Xu , Changyou Gao","doi":"10.1016/j.actbio.2024.12.015","DOIUrl":"10.1016/j.actbio.2024.12.015","url":null,"abstract":"<div><div>Hydrogel microparticles (HMPs) have many advantages for biomedical applications, particularly for minimally invasive therapy, for example, acute lung injury (ALI) that is characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators in the microenvironment. In this study, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were designed and prepared by using a membrane emulsification device. The HMPs were composed of double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal linkages and unsaturated double bonds. Surface-coating of inflammatory macrophage (M1) cell membranes was performed to obtain the membrane-coated HBPAK HMPs (mem HMPs) via electrostatic force. The mem HMPs exhibited strong ROS-scavenging and anti-inflammatory properties both <em>in vitro</em> and <em>in vivo</em>. After administered by inhalation in an ALI mouse model, the mem HMPs reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation. Our results suggest that the mem HMPs could serve as a potential therapeutic platform for treating inflammatory diseases with high efficiency.</div></div><div><h3>Statement of significance</h3><div>Hydrogel microparticles (HMPs) with minimally invasive delivery are advantageous for acute lung injury (ALI) characterized by high levels of reactive oxygen species (ROS) and pro-inflammatory mediators. Herein, ROS-scavenging and pro-inflammatory cytokine-neutralizing HMPs were prepared by copolymerizing double bond-modified hyaluronic acid and ROS-cleavable hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) containing thioketal bonds and unsaturated double bonds in a membrane emulsification device. The HMPs covered with inflammatory macrophage (M1) cell membranes (mem HMPs) exhibited strong ROS-scavenging and anti-inflammation properties, reduced neutrophil infiltration and tissue oxidative damage, thereby alleviating lung inflammation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 409-418"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796677","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.12.029
Janina Stadter , Andreas Hoess , Hans Leemhuis , Aaron Herrera , Rebecca Günther , Simone Cho , Stephanie Diederich , Gabriela Korus , Richard Frank Richter , Ansgar Petersen
Regeneration of large bone defects remains a clinical challenge until today. While existing biomaterials are predominantly addressing bone healing via direct, intramembranous ossification (IO), bone tissue formation via a cartilage phase, so-called endochondral ossification (EO) has been shown to be a promising alternative strategy. However, pure biomaterial approaches for EO induction are sparse and the knowledge how material components can have bioactive contribution to the required cartilage formation is limited. Here, we combined a previously developed purely architecture-driven biomaterial approach with the release of therapeutic metal ions from tailored silicate microparticles. The delivery platform was free of calcium phosphates (CaP) that are known to support IO but not EO and was employed for the release of lithium (Li), magnesium (Mg), strontium (Sr) or zinc (Zn) ions. We identified an ion-specific cellular response in which certain metal ions strongly enhanced cell recruitment into the material and showed superior chondrogenesis and deposition collagen II by human mesenchymal stromal cells (MSCs). At the same time, in some cases microparticle incorporation altered the mechanical properties of the biomaterial with consequences for cell-induced biomaterial contraction and scaffold wall deformation. Collectively, the results suggest that the incorporation of metal-doped silicate microparticles has the potential to further improve the bioactivity of architectured biomaterials for bone defect healing via EO.
Statement of significance
Endochondral bone healing, a process that resembles embryonic skeletal development, has gained prominence in regenerative medicine. However, most therapeutic biomaterial strategies are not optimized for endochondral bone healing but instead target direct bone formation through IO. Here, we report on a novel approach to accelerate biomaterial-guided endochondral bone healing by combining cell-guiding collagen scaffolds with therapeutic metal-doped silicate microparticles. While other strategies, such as hypoxia-mimic drugs and iron-chelating biomaterials, have been documented in the literature before to enhance EO, our approach uniquely implements enhanced bioactivity into a previously developed biomaterial strategy for bone defect regeneration. Enhanced cell recruitment into the material and more pronounced chondrogenesis were observed for specific hybrid scaffold formulations, suggesting a high relevance of this new biomaterial for improved endochondral bone healing.
直到今天,大面积骨缺损的再生仍然是一项临床挑战。虽然现有的生物材料主要通过直接的膜内骨化(IO)来解决骨愈合问题,但通过软骨阶段(即所谓的软骨内骨化(EO))形成骨组织已被证明是一种很有前景的替代策略。然而,用于诱导 EO 的纯生物材料方法并不多见,人们对材料成分如何对所需的软骨形成具有生物活性的了解也很有限。在这里,我们将之前开发的纯结构驱动生物材料方法与从定制硅酸盐微粒中释放治疗性金属离子相结合。该递送平台不含已知支持 IO 但不支持 EO 的磷酸钙 (CaP),并用于释放锂 (Li)、镁 (Mg)、锶 (Sr) 或锌 (Zn) 离子。我们发现了一种离子特异性细胞反应,其中某些金属离子能强烈促进细胞进入材料,并显示出人类间充质基质细胞(MSCs)具有卓越的软骨生成和胶原蛋白 II 沉积能力。同时,在某些情况下,微颗粒的加入改变了生物材料的机械性能,对细胞诱导的生物材料收缩和支架壁变形产生了影响。总之,研究结果表明,掺金属硅酸盐微颗粒的加入有可能进一步提高架构生物材料的生物活性,从而通过环氧乙烷促进骨缺损愈合。意义说明:软骨内骨愈合是一种类似于胚胎骨骼发育的过程,在再生医学中已占据重要地位。然而,大多数生物材料治疗策略并未针对软骨内骨愈合进行优化,而是通过膜内骨化直接形成骨。在此,我们报告了一种新方法,通过将细胞引导胶原支架与治疗性掺金属硅酸盐微颗粒相结合,加速生物材料引导的软骨内骨愈合。虽然之前已有文献记载了其他策略(如缺氧模拟药物和铁螯合生物材料)来增强软骨内骨化,但我们的方法将增强生物活性独特地应用到了之前开发的骨缺损再生生物材料策略中。在特定的混合支架配方中,观察到细胞进入材料的能力增强,软骨生成更加明显,这表明这种新型生物材料对改善软骨内骨愈合具有重要意义。
{"title":"Incorporation of metal-doped silicate microparticles into collagen scaffolds combines chemical and architectural cues for endochondral bone healing","authors":"Janina Stadter , Andreas Hoess , Hans Leemhuis , Aaron Herrera , Rebecca Günther , Simone Cho , Stephanie Diederich , Gabriela Korus , Richard Frank Richter , Ansgar Petersen","doi":"10.1016/j.actbio.2024.12.029","DOIUrl":"10.1016/j.actbio.2024.12.029","url":null,"abstract":"<div><div>Regeneration of large bone defects remains a clinical challenge until today. While existing biomaterials are predominantly addressing bone healing via direct, intramembranous ossification (IO), bone tissue formation via a cartilage phase, so-called endochondral ossification (EO) has been shown to be a promising alternative strategy. However, pure biomaterial approaches for EO induction are sparse and the knowledge how material components can have bioactive contribution to the required cartilage formation is limited. Here, we combined a previously developed purely architecture-driven biomaterial approach with the release of therapeutic metal ions from tailored silicate microparticles. The delivery platform was free of calcium phosphates (CaP) that are known to support IO but not EO and was employed for the release of lithium (Li), magnesium (Mg), strontium (Sr) or zinc (Zn) ions. We identified an ion-specific cellular response in which certain metal ions strongly enhanced cell recruitment into the material and showed superior chondrogenesis and deposition collagen II by human mesenchymal stromal cells (MSCs). At the same time, in some cases microparticle incorporation altered the mechanical properties of the biomaterial with consequences for cell-induced biomaterial contraction and scaffold wall deformation. Collectively, the results suggest that the incorporation of metal-doped silicate microparticles has the potential to further improve the bioactivity of architectured biomaterials for bone defect healing via EO.</div></div><div><h3>Statement of significance</h3><div>Endochondral bone healing, a process that resembles embryonic skeletal development, has gained prominence in regenerative medicine. However, most therapeutic biomaterial strategies are not optimized for endochondral bone healing but instead target direct bone formation through IO. Here, we report on a novel approach to accelerate biomaterial-guided endochondral bone healing by combining cell-guiding collagen scaffolds with therapeutic metal-doped silicate microparticles. While other strategies, such as hypoxia-mimic drugs and iron-chelating biomaterials, have been documented in the literature before to enhance EO, our approach uniquely implements enhanced bioactivity into a previously developed biomaterial strategy for bone defect regeneration. Enhanced cell recruitment into the material and more pronounced chondrogenesis were observed for specific hybrid scaffold formulations, suggesting a high relevance of this new biomaterial for improved endochondral bone healing.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 260-278"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824977","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.12.038
Hui Rong , Shupeng Sun , Manhua Lu , Yiqun Zhang , Lingyuan Liu , Ziwei Guo , Zimeng Zhang , Zhanpeng Ye , Jianhua Zhang , Budong Chen , Shuangyang Li , Anjie Dong
The dura trauma or large defects due to neurosurgical procedures can result in potential complications. Dural replacements have proven effective to reduce the risk of seizures, meningitis, cerebrospinal fluid leakage, cerebral herniation, and infection. Although various artificial dural patches have been developed, addressing iatrogenic infections and cerebral adhesions resulting from patches implantation remains a challenge. This study employed a network interpenetration modification strategy to introduce super-hydrophilic and super-lubricity zwitterionic hydrogel coatings on polyurethane Neuro-Patch® (NP®) dura mater patch. The successful modification with the hydrogel coating preserved the intrinsic properties of the NP®, such as their anti-leakage and tensile strength capabilities, while effectively reducing biofouling on the surface of the patches. Additionally, by constructing subdural implantation for each dura mater substitute in rabbits, we observed that artificial dura mater patches modified with the hydrogel coating effectively reduced the incidence of postoperative cerebral adhesions and infections. This suggests a promising application prospect of the hydrogel coating in dural repair.
Statement of significance
The development of dural substitutes with anti-leakage, anti-adhesion and anti-infection functions is the key to the treatment of dural defects and cerebrospinal fluid leakage during trauma or neurosurgery. In this study, the amphoteric ionic hydrogel coating was firmly modified on the surface of polyurethane with a mild modification process to give the patch super-hydrophilic and super-lubricating properties. The adhesion of non-specific proteins and bacteria is effectively reduced. The rabbit dural defect repair model showed that the introduction of zwitterionic hydrogel coating effectively reduced the occurrence of postoperative infection, and no tissue adhesion was observed. Taken together, this study offers a promising way to enhance the performance of artificial dural patches, potentially benefiting patients undergoing neurosurgery.
{"title":"Super-hydrophilic and super-lubricating Zwitterionic hydrogel coatings coupled with polyurethane to reduce postoperative dura mater adhesions and infections","authors":"Hui Rong , Shupeng Sun , Manhua Lu , Yiqun Zhang , Lingyuan Liu , Ziwei Guo , Zimeng Zhang , Zhanpeng Ye , Jianhua Zhang , Budong Chen , Shuangyang Li , Anjie Dong","doi":"10.1016/j.actbio.2024.12.038","DOIUrl":"10.1016/j.actbio.2024.12.038","url":null,"abstract":"<div><div>The dura trauma or large defects due to neurosurgical procedures can result in potential complications. Dural replacements have proven effective to reduce the risk of seizures, meningitis, cerebrospinal fluid leakage, cerebral herniation, and infection. Although various artificial dural patches have been developed, addressing iatrogenic infections and cerebral adhesions resulting from patches implantation remains a challenge. This study employed a network interpenetration modification strategy to introduce super-hydrophilic and super-lubricity zwitterionic hydrogel coatings on polyurethane Neuro-Patch® (NP®) dura mater patch. The successful modification with the hydrogel coating preserved the intrinsic properties of the NP®, such as their anti-leakage and tensile strength capabilities, while effectively reducing biofouling on the surface of the patches. Additionally, by constructing subdural implantation for each dura mater substitute in rabbits, we observed that artificial dura mater patches modified with the hydrogel coating effectively reduced the incidence of postoperative cerebral adhesions and infections. This suggests a promising application prospect of the hydrogel coating in dural repair.</div></div><div><h3>Statement of significance</h3><div>The development of dural substitutes with anti-leakage, anti-adhesion and anti-infection functions is the key to the treatment of dural defects and cerebrospinal fluid leakage during trauma or neurosurgery. In this study, the amphoteric ionic hydrogel coating was firmly modified on the surface of polyurethane with a mild modification process to give the patch super-hydrophilic and super-lubricating properties. The adhesion of non-specific proteins and bacteria is effectively reduced. The rabbit dural defect repair model showed that the introduction of zwitterionic hydrogel coating effectively reduced the occurrence of postoperative infection, and no tissue adhesion was observed. Taken together, this study offers a promising way to enhance the performance of artificial dural patches, potentially benefiting patients undergoing neurosurgery.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 206-217"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831190","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.12.031
Adwait A. Trikanad , Phani Saketh Dasika , Hoover Pantoja-Sánchez , Ximena E. Bernal , Pablo D. Zavattieri
Unlike organisms equipped with tympanal ears, mosquitoes hear using their antennae, which are lightweight sensory structures capable of detecting sound. Here, we study the antennae of two species — Aedes aegypti and Uranotaenia lowii — known to use hearing for different functions. Through the use of geometrically comprehensive computational models, we find that architectural features in the mosquito antenna provide mechanisms that promote the detection of species and sex specific acoustic targets amidst the non-target signals produced by their own wingbeats. Structurally, we find that the increased surface area of sensory hairs provides enhanced sensitivity while the tapering effect of intersegmental variation affects the tuning response. These features result in the highest antennal sensitivity through vibration at specific natural frequency modes that correspond to frequencies associated with their acoustic targets.
Statement of Significance
Our study provides valuable insights into the remarkable architectural design of mosquito antennae and its role in auditory adaptations. By dissecting the intricate geometry of antennal architecture in Aedes aegypti and Uranotaenia lowii, we uncover mechanisms that enhance sensitivity to specific acoustic cues while mitigating interference from wingbeat noise. This research builds upon and extends the existing understanding, providing a deeper comprehension of how mosquitoes navigate their acoustic environment. Our findings have significant implications for understanding sensory adaptations in insects and may inspire the development of bioinspired sensing technologies. We believe our work will interest a broad audience by offering new perspectives on the intersection of biomechanics and sensory biology, which can also find applications in the design of bioinspired architected materials.
{"title":"Mechanistic insights into mosquito antennal architecture for auditory adaptations","authors":"Adwait A. Trikanad , Phani Saketh Dasika , Hoover Pantoja-Sánchez , Ximena E. Bernal , Pablo D. Zavattieri","doi":"10.1016/j.actbio.2024.12.031","DOIUrl":"10.1016/j.actbio.2024.12.031","url":null,"abstract":"<div><div>Unlike organisms equipped with tympanal ears, mosquitoes hear using their antennae, which are lightweight sensory structures capable of detecting sound. Here, we study the antennae of two species — <em>Aedes aegypti</em> and <em>Uranotaenia lowii</em> — known to use hearing for different functions. Through the use of geometrically comprehensive computational models, we find that architectural features in the mosquito antenna provide mechanisms that promote the detection of species and sex specific acoustic targets amidst the non-target signals produced by their own wingbeats. Structurally, we find that the increased surface area of sensory hairs provides enhanced sensitivity while the tapering effect of intersegmental variation affects the tuning response. These features result in the highest antennal sensitivity through vibration at specific natural frequency modes that correspond to frequencies associated with their acoustic targets.</div></div><div><h3>Statement of Significance</h3><div>Our study provides valuable insights into the remarkable architectural design of mosquito antennae and its role in auditory adaptations. By dissecting the intricate geometry of antennal architecture in <em>Aedes aegypti</em> and <em>Uranotaenia lowii</em>, we uncover mechanisms that enhance sensitivity to specific acoustic cues while mitigating interference from wingbeat noise. This research builds upon and extends the existing understanding, providing a deeper comprehension of how mosquitoes navigate their acoustic environment. Our findings have significant implications for understanding sensory adaptations in insects and may inspire the development of bioinspired sensing technologies. We believe our work will interest a broad audience by offering new perspectives on the intersection of biomechanics and sensory biology, which can also find applications in the design of bioinspired architected materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 165-174"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824613","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}
Pub Date : 2025-01-15DOI: 10.1016/j.actbio.2024.12.019
Masoud Yusefi , Emmanouil Agrafiotis , Peter Regitnig , Günther Laufer , Gerhard Sommer , Gerhard A. Holzapfel , Heinrich Mächler
<div><div>This study aims to assess the outcomes of therapeutic options for aortic arch pathologies by comparing thoracic endovascular aortic repair (TEVAR) with open arch replacement (OAR) using woven polyester grafts from a mechanical and biomechanical perspective, with emphasis on <em>ex vivo</em> perfused human thoracic aortas reproducing heart rate and stroke volume conditions. Eleven non-diseased thoracic aortas from human cadavers were divided into TEVAR (<span><math><mrow><mi>n</mi><mo>=</mo><mn>5</mn></mrow></math></span>) and OAR (<span><math><mrow><mi>n</mi><mo>=</mo><mn>6</mn></mrow></math></span>) and tested using a custom-built mock circulation loop. Pressure, diameter, and stroke volume were monitored during perfusion before and after the intervention. Samples undergoing TEVAR showed a higher ascending systolic pressure post-intervention than OAR (TEVAR: <span><math><mrow><mn>137</mn><mo>±</mo><mn>9</mn></mrow></math></span> <!--> <!-->mmHg vs OAR: <span><math><mrow><mn>126</mn><mo>±</mo><mn>6</mn></mrow></math></span> <!--> <!-->mmHg, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>017</mn></mrow></math></span>). After the intervention, a significant discrepancy in the mean pressure differences between the ascending and descending aorta <span><math><mrow><mi>Δ</mi><mi>P</mi></mrow></math></span> was observed (TEVAR: <span><math><mrow><mn>9</mn><mo>±</mo><mn>3</mn></mrow></math></span> <!--> <!-->mmHg vs OAR: <span><math><mrow><mn>1</mn><mo>±</mo><mn>2</mn></mrow></math></span> <!--> <!-->mmHg, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>004</mn></mrow></math></span>). Input impedance at zero frequency, approximating Windkessel resistance, was higher for TEVAR than for OAR (TEVAR: <span><math><mrow><mn>1</mn><mo>.</mo><mn>78</mn><mo>±</mo><mn>0</mn><mo>.</mo><mn>04</mn></mrow></math></span> vs OAR: <span><math><mrow><mn>1</mn><mo>.</mo><mn>66</mn><mo>±</mo><mn>0</mn><mo>.</mo><mn>03</mn></mrow></math></span> <!--> <!-->mmHg<!--> <!-->s/ml, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>004</mn></mrow></math></span>). A correlation was found between the resistance and the negative peak of the time-normalized wave intensity analysis (Kendall’s coefficient <span><math><mrow><mi>τ</mi><mo>=</mo><mo>−</mo><mn>0</mn><mo>.</mo><mn>35</mn></mrow></math></span> and <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>023</mn></mrow></math></span>). Another correlation was observed between resistance and <span><math><mrow><mi>Δ</mi><mi>P</mi></mrow></math></span> (<span><math><mrow><mi>τ</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>51</mn></mrow></math></span>, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>001</mn></mrow></math></span>). Looking at the replication of heart rate and stroke volume over the course of the study, the observed differences can largely be attributed to the type of intervention. The results suggest that TEVAR has adverse effects compared to OAR, particu
本研究旨在通过从机械和生物力学角度比较胸腔内主动脉血管修复术(TEVAR)和使用编织聚酯移植物的开放式主动脉弓置换术(OAR),评估主动脉弓病变治疗方案的效果,重点是在体外灌注的人体胸主动脉上再现心率和每搏容量条件。来自人体尸体的 11 根无病变的胸主动脉被分为 TEVAR(5 根)和 OAR(6 根),并使用定制的模拟循环回路进行测试。在干预前后的灌注过程中,对压力、直径和每搏容积进行了监测。接受 TEVAR 的样本在干预后的升支收缩压高于 OAR(TEVAR:137±9mmHg vs OAR:126±6mmHg,P=0.017)。干预后,升主动脉和降主动脉的平均压力差ΔP有明显差异(TEVAR:9±3mmHg vs OAR:1±2mmHg,P=0.004)。TEVAR 的零频率输入阻抗(近似 Windkessel 阻力)高于 OAR(TEVAR:1.78±0.04 vs OAR:1.66±0.03mmHgs/ml,P=0.004)。阻力与时间标准化波强度分析的负峰值之间存在相关性(肯德尔系数τ=-0.35,P=0.023)。阻力与 ΔP 之间也存在相关性(τ=0.51,P=0.001)。从研究过程中心率和搏出量的重复情况来看,观察到的差异在很大程度上可归因于干预类型。结果表明,TEVAR与OAR相比具有不利影响,尤其是在左心室后负荷方面。临床医生在决定是否进行 TEVAR 时,应考虑到后负荷增加和波动力改变的可能性,尤其是对已存在心血管疾病的患者。
{"title":"TEVAR versus open aortic arch replacement in ex vivo perfused human thoracic aortas","authors":"Masoud Yusefi , Emmanouil Agrafiotis , Peter Regitnig , Günther Laufer , Gerhard Sommer , Gerhard A. Holzapfel , Heinrich Mächler","doi":"10.1016/j.actbio.2024.12.019","DOIUrl":"10.1016/j.actbio.2024.12.019","url":null,"abstract":"<div><div>This study aims to assess the outcomes of therapeutic options for aortic arch pathologies by comparing thoracic endovascular aortic repair (TEVAR) with open arch replacement (OAR) using woven polyester grafts from a mechanical and biomechanical perspective, with emphasis on <em>ex vivo</em> perfused human thoracic aortas reproducing heart rate and stroke volume conditions. Eleven non-diseased thoracic aortas from human cadavers were divided into TEVAR (<span><math><mrow><mi>n</mi><mo>=</mo><mn>5</mn></mrow></math></span>) and OAR (<span><math><mrow><mi>n</mi><mo>=</mo><mn>6</mn></mrow></math></span>) and tested using a custom-built mock circulation loop. Pressure, diameter, and stroke volume were monitored during perfusion before and after the intervention. Samples undergoing TEVAR showed a higher ascending systolic pressure post-intervention than OAR (TEVAR: <span><math><mrow><mn>137</mn><mo>±</mo><mn>9</mn></mrow></math></span> <!--> <!-->mmHg vs OAR: <span><math><mrow><mn>126</mn><mo>±</mo><mn>6</mn></mrow></math></span> <!--> <!-->mmHg, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>017</mn></mrow></math></span>). After the intervention, a significant discrepancy in the mean pressure differences between the ascending and descending aorta <span><math><mrow><mi>Δ</mi><mi>P</mi></mrow></math></span> was observed (TEVAR: <span><math><mrow><mn>9</mn><mo>±</mo><mn>3</mn></mrow></math></span> <!--> <!-->mmHg vs OAR: <span><math><mrow><mn>1</mn><mo>±</mo><mn>2</mn></mrow></math></span> <!--> <!-->mmHg, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>004</mn></mrow></math></span>). Input impedance at zero frequency, approximating Windkessel resistance, was higher for TEVAR than for OAR (TEVAR: <span><math><mrow><mn>1</mn><mo>.</mo><mn>78</mn><mo>±</mo><mn>0</mn><mo>.</mo><mn>04</mn></mrow></math></span> vs OAR: <span><math><mrow><mn>1</mn><mo>.</mo><mn>66</mn><mo>±</mo><mn>0</mn><mo>.</mo><mn>03</mn></mrow></math></span> <!--> <!-->mmHg<!--> <!-->s/ml, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>004</mn></mrow></math></span>). A correlation was found between the resistance and the negative peak of the time-normalized wave intensity analysis (Kendall’s coefficient <span><math><mrow><mi>τ</mi><mo>=</mo><mo>−</mo><mn>0</mn><mo>.</mo><mn>35</mn></mrow></math></span> and <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>023</mn></mrow></math></span>). Another correlation was observed between resistance and <span><math><mrow><mi>Δ</mi><mi>P</mi></mrow></math></span> (<span><math><mrow><mi>τ</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>51</mn></mrow></math></span>, <span><math><mrow><mi>p</mi><mo>=</mo><mn>0</mn><mo>.</mo><mn>001</mn></mrow></math></span>). Looking at the replication of heart rate and stroke volume over the course of the study, the observed differences can largely be attributed to the type of intervention. The results suggest that TEVAR has adverse effects compared to OAR, particu","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 140-150"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824773","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}