Fahmida Habib Nabila, Rashedul Islam, Li Yamin, Kawaguchi Yoshirou, Rie Wakabayashi, Noriho Kamiya, Muhammad Moniruzzaman, Masahiro Goto
{"title":"Transdermal Insulin Delivery Using Ionic Liquid-Mediated Nanovesicles for Diabetes Treatment.","authors":"Fahmida Habib Nabila, Rashedul Islam, Li Yamin, Kawaguchi Yoshirou, Rie Wakabayashi, Noriho Kamiya, Muhammad Moniruzzaman, Masahiro Goto","doi":"10.1021/acsbiomaterials.4c02000","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02000","url":null,"abstract":"<p><p>Transdermal insulin delivery is a promising method for diabetes management, providing the potential for controlled, sustained release and prolonged insulin effectiveness. However, the large molecular weight of insulin hinders its passive absorption through the stratum corneum (SC) of the skin, and high doses of insulin are required, which limits the commercial viability. We developed ethosome (ET) and <i>trans</i>-ethosome (TET) nanovesicle formulations containing a biocompatible lipid-based ionic liquid, [EDMPC][Lin], dissolved in 35% ethanol. TET formulations were obtained by adding isopropyl myristate (IPM), Tween-80, or Span-20 as surfactants to ET formulations. Dynamic light scattering, ζ-potential, transmission electron microscopy, and confocal laser scanning microscopy studies revealed that the nanovesicles had a stable particle size. The formulations remained stable at 4 °C for more than 3 months. ET and TET formulations containing IPM (TET1) significantly (<i>p</i> < 0.0001) enhanced the transdermal penetration of FITC-tagged insulin (FITC-Ins) in both mouse and pig skin, compared with that of the control FITC-Ins solution and other TET formulations, by altering the molecular structure of the SC layer. These nanovesicles were found to be biocompatible and nonirritants (cell viability >80%) in the <i>in vitro</i> and <i>in vivo</i> studies on three-dimensional (3D) artificial human skin and a diabetic mouse model, respectively. The ET and TET1 formulations were applied to the skin of diabetic mice at an insulin dosage of 30 IU/kg. The nanovesicle formulations significantly reduced blood glucose levels (BGLs) compared with the initial high BGL value (>150 mg/dL). The nanovesicle-treated mice maintained low BGLs for over 15 h, as opposed to only 2 h in the injection group. The ET and TET1 formulations reduced the BGLs by 62 and 34%, respectively, of the initial value. These ET and TET1 formulations have a high potential for use in commercial transdermal insulin patches, enhancing comfort and adherence in diabetes treatment.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathryn M Luly, Jordan J Green, Joel C Sunshine, Stephany Y Tzeng
{"title":"Correction to \"Biomaterial-Mediated Genetic Reprogramming of Merkel Cell Carcinoma and Melanoma Leads to Targeted Cancer Cell Killing <i>In Vitro</i> and <i>In Vivo</i>\".","authors":"Kathryn M Luly, Jordan J Green, Joel C Sunshine, Stephany Y Tzeng","doi":"10.1021/acsbiomaterials.4c02308","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02308","url":null,"abstract":"","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdullah-Bin Siddique, Keith A Williams, Nathan S Swami
{"title":"Nanogrooved Elastomeric Diaphragm Arrays for Assessment of Cardiomyocytes under Synergistic Effects of Circular Mechanical Stimuli and Electrical Conductivity to Enhance Intercellular Communication.","authors":"Abdullah-Bin Siddique, Keith A Williams, Nathan S Swami","doi":"10.1021/acsbiomaterials.4c01298","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01298","url":null,"abstract":"<p><p>Cardiovascular diseases remain the leading cause of mortality, necessitating advancements in <i>in vitro</i> cardiac tissue engineering platforms for improved disease modeling, drug screening, and regenerative therapies. The chief challenge to recapitulating the beating behavior of cardiomyocytes is creation of the circular stress profile experienced by hollow organs in the natural heart due to filling pressure and integrated strategies for intercellular communication to promote cell-to-cell connections. We present a platform featuring addressable arrays of nanogrooved polydimethylsiloxane (PDMS) diaphragms for cell alignment and circular mechanical stimulation, with embedded silver nanowires (AgNWs) for electrical cues, so that cardiomyocyte functionality can be assessed under these synergistic influences. Central to our innovation is a two-layer PDMS diaphragm design that electrically isolates the liquid metal (EGaIn) strain sensor in the bottom layer to enable detection and control of mechanical stimulation from conductive portions of embedded AgNWs in the top layer that supports cardiomyocyte culture and communication. In this manner, through localized detection and control of the circular mechanical stimulation, the essential role of multiaxial stretching on cardiomyocyte function is elucidated based on their contractility, sarcomere length, and connexin-43 expression. This <i>in vitro</i> platform can potentially transform cardiac tissue engineering, drug screening, and precision medicine approaches.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ziliang Zhang, Zhi Zheng, Yuxin Gao, Wang Li, Xiaoyu Zhang, Huan Luo, Shouqin Lü, Yu Du, Yan Zhang, Ning Li, Mian Long
{"title":"Developing a Flow-Resistance Module for Elucidating Cell Mechanotransduction on Multiple Shear Stresses.","authors":"Ziliang Zhang, Zhi Zheng, Yuxin Gao, Wang Li, Xiaoyu Zhang, Huan Luo, Shouqin Lü, Yu Du, Yan Zhang, Ning Li, Mian Long","doi":"10.1021/acsbiomaterials.4c01604","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01604","url":null,"abstract":"<p><p>Fluid shear stress plays a pivotal role in regulating cellular behaviors, maintaining tissue homeostasis, and driving disease progression. Cells in various tissues are specifically adapted to physiological levels of shear stress and exhibit sensitivity to variations in its magnitude, highlighting the requirement for a comprehensive understanding of cellular responses to both physiologically and pathologically relevant levels of shear stress. In this study, we developed an independent upstream flow-resistance module with high fluidic resistances comprising three microchannels. The validity of the flow-resistance module was confirmed via computational fluid dynamics (CFD) simulations and flow calibration experiments, resulting in the generation of steady wall shear stresses ranging from 0.06 to 11.57 dyn/cm<sup>2</sup> within the interconnected cell culture chips. Gene expression profiles, cytoskeletal remodeling, and morphological changes, as well as Yes-associated protein (YAP) nuclear translocation, were investigated in response to various shear stresses to authenticate the reliability of our experimental platform, indicating an increasing trend as the shear stress increases, reaching its maximum at various shear stresses. Our findings suggest that this flow-resistance module can be readily employed for precise characterization of cellular responses under various shear stresses.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chang Liu, Zhengjiang Cao, Li Li, Qingyin Li, Chunle Zhang, Yunbing Wang, Linhua Li, Ping Fu
{"title":"Self-Assembled Pt/Honokiol Nanomicelles for the Treatment of Sepsis-Associated Acute Kidney Injury.","authors":"Chang Liu, Zhengjiang Cao, Li Li, Qingyin Li, Chunle Zhang, Yunbing Wang, Linhua Li, Ping Fu","doi":"10.1021/acsbiomaterials.4c01852","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01852","url":null,"abstract":"<p><p>Sepsis is a severe and complex systemic infection that can result in multiple organ dysfunction. Sepsis-associated acute kidney injury (SAKI), caused by inflammatory response, oxidative stress, and cellular apoptosis, is a common complication that seriously impacts patient survival rates. Herein, a potent and novel metal-polyphenol nanomicelle can be efficiently self-assembled with Pt<sup>4+</sup> and honokiol (HK) by the chelation, π-π conjugation, hydrophobic action, and the surfactant properties of Tween-80. These nanomicelles not only enhance drug bioavailability (encapsulation rates: Pt─49%, HK─70%) and reduce drug toxicity (safety dose: <20 μg/g) but also improve targeting toward damaged renal tissues. Furthermore, Pt<sup>4+</sup> and HK in the nanomicelles exert a synergistic physiological effect by scavenging free radicals to alleviate oxidative damage, inhibiting macrophage activation and the release of inflammatory factors to regulate inflammation, and displaying broad-spectrum antimicrobial activity to control infection. These actions collectively protect renal tissue and restore its functionality. Here, we constructed metal-polyphenol nanomicelles (Pt/HK-NMs) via ingenious and efficient self-assembly, providing a new strategy to compensate for deficiencies in the hemodialysis and antibiotic treatment of SAKI.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hierarchical Collagen/Apatite Co-assembly for Injection of Mineralized Fibrillar Tissue Analogues.","authors":"Milena Lama, Marion Merle, Elora Bessot, Camila Bussola Tovani, Guillaume Laurent, Nicole Bouland, Halima Kerdjoudj, Thierry Azaïs, Guylaine Ducouret, Tissiana Bortolotto, Nadine Nassif","doi":"10.1021/acsbiomaterials.4c02115","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02115","url":null,"abstract":"<p><p>Mineralized biological tissues rich in type I collagen (e.g., bone and dentin) exhibit complex anisotropic suprafibrillar organizations in which the organic and inorganic moieties are intimately coassembled over several length scales. Above a critical size, a defect in such tissue cannot be self-repaired. Biomimetic materials with a composition and microstructure similar to that of bone have been shown to favorably influence bone regeneration. This highlights the value of developing a similar formulation in an injectable form to enable minimally invasive techniques. Here, we report on the fabrication and application potential of an injectable collagen/CHA (carbonated hydroxyapatite) cell-free hydrogel. The organic part consists of spray-dried nondenatured and dense collagen microparticles, while the inorganic part consists of biomimetic apatite mineral. By mixing both powders at desired tissue-like ratios with an aqueous solvent in one step, spontaneous co-self-assembly occurs, leading to the formation of a mineralized matrix with suprafibrillar tissue-like features thanks to the induced liquid crystalline properties of collagen on one hand and apatite on the other hand. When injected into soft tissue, the mineralized collagen hydrogel free of chemical cross-linking agents exhibits suitable cohesion and is biocompatible. Preliminary in vitro tests in a tooth cavity model show its integration onto dentin with a biomimetic interface. Based on the results, this versatile injectable mineralized collagen hydrogel shows promising potential as a biomaterial for bone tissue repair and mineralized tissue-like ink for bioprinting applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara Mihandoost, Sima Rezvantalab, Roger M Pallares, Volkmar Schulz, Fabian Kiessling
{"title":"A Generative Adversarial Network Approach to Predict Nanoparticle Size in Microfluidics.","authors":"Sara Mihandoost, Sima Rezvantalab, Roger M Pallares, Volkmar Schulz, Fabian Kiessling","doi":"10.1021/acsbiomaterials.4c01423","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01423","url":null,"abstract":"<p><p>To achieve precise control over the properties and performance of nanoparticles (NPs) in a microfluidic setting, a profound understanding of the influential parameters governing the NP size is crucial. This study specifically delves into poly(lactic-<i>co</i>-glycolic acid) (PLGA)-based NPs synthesized through microfluidics that have been extensively explored as drug delivery systems (DDS). A comprehensive database, containing more than 11 hundred data points, is curated through an extensive literature review, identifying potential effective features. Initially, we employed a tabular generative adversarial network (TGAN) to enhance data sets, increasing the reliability of the obtained results and elevating prediction accuracy. Subsequently, NP size prediction was performed using different machine learning (ML) techniques including decision tree (DT), random forest (RF), deep neural networks (DNN), linear regression (LR), support vector regression (SVR), and gradient boosting (GB). Among these ensembles, DT emerges as the most accurate algorithm, yielding an average prediction error of 8%. Further simulations underscore the pivotal role of the synthesis method, poly(vinyl alcohol) (PVA) concentration, and lactide-to-glycolide (LA/GA) ratio of PLGA copolymers as the primary determinants influencing NP size.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaojun Zhou, Shuo Chen, Andrij Pich, Chuanglong He
{"title":"Advanced Bioresponsive Drug Delivery Systems for Promoting Diabetic Vascularized Bone Regeneration.","authors":"Xiaojun Zhou, Shuo Chen, Andrij Pich, Chuanglong He","doi":"10.1021/acsbiomaterials.4c02037","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02037","url":null,"abstract":"<p><p>The treatment of bone defects in diabetes mellitus (DM) patients remains a major challenge since the diabetic microenvironments significantly impede bone regeneration. Many abnormal factors including hyperglycemia, elevated oxidative stress, increased inflammation, imbalanced osteoimmune, and impaired vascular system in the diabetic microenvironment will result in a high rate of impaired, delayed, or even nonhealing events of bone tissue. Stimuli-responsive biomaterials that can respond to endogenous biochemical signals have emerged as effective therapeutic systems to treat diabetic bone defects via the combination of microenvironmental regulation and enhanced osteogenic capacity. Following the natural bone healing processes, coupling of angiogenesis and osteogenesis by advanced bioresponsive drug delivery systems has proved to be of significant approach for promoting bone repair in DM. In this Review, we have systematically summarized the mechanisms and therapeutic strategies of DM-induced impaired bone healing, outlined the bioresponsive design for drug delivery systems, and highlighted the vascularization strategies for promoting bone regeneration. Accordingly, we then overview the recent advances in developing bioresponsive drug delivery systems to facilitate diabetic vascularized bone regeneration by remodeling the microenvironment and modulating multiple regenerative cues. Furthermore, we discuss the development of adaptable drug delivery systems with unique features for guiding DM-associated bone regeneration in the future.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Momoko Sakata, Yuki Imaizumi, Takumi Iwasawa, Kazunori Kato, Tatsuro Goda
{"title":"Semiconductor Transistor-Based Detection of Epithelial-Mesenchymal Transition via Weak Acid-Induced Proton Perturbation.","authors":"Momoko Sakata, Yuki Imaizumi, Takumi Iwasawa, Kazunori Kato, Tatsuro Goda","doi":"10.1021/acsbiomaterials.4c01707","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01707","url":null,"abstract":"<p><p>Developing new detection methods for the epithelial-mesenchymal transition (EMT), where epithelial cells acquire mesenchymal traits, is crucial for understanding tissue development, cancer invasion, and metastasis. Conventional <i>in vitro</i> EMT evaluation methods like permeability measurements are time-consuming and low-throughput, while the transepithelial electrical resistance measurements struggle to differentiate between cell membrane damage and tight junction (TJ) loss and are affected by cell proliferation. In this study, we developed a pH perturbation method to detect TJ barrier disruption during epithelial EMT by sensing proton leakage induced by a weak acid using a pH-responsive semiconductor. Mardin-Darby canine kidney (MDCK) epithelial cell sheets cultured on an ion-sensitive field effect transistor's gate insulator were induced into EMT by exposure to the cytokine transforming growth factor-β1 (TGF-β). Our pH perturbation method successfully detected EMT in MDCK sheets at a TGF-β concentration one-tenth of that required for conventional methods. The high sensitivity and selectivity arise from using minimal protons as indicators of TJ barrier disruption. TGF-β-induced EMT detection results using our method align with EMT-related gene and protein expression data. In drug screening with EMT inhibitors, this novel method showed similar trends to conventional ones. The pH perturbation method enables highly sensitive, real-time EMT detection, contributing to elucidating biological phenomena and pharmaceutical development.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marko S Chavez, Magdalene A MacLean, Nir Sukenik, Sukrampal Yadav, Carolyn Marks, Mohamed Y El-Naggar
{"title":"Synthesis of Palladium Nanoparticles by Electrode-Respiring <i>Geobacter sulfurreducens</i> Biofilms.","authors":"Marko S Chavez, Magdalene A MacLean, Nir Sukenik, Sukrampal Yadav, Carolyn Marks, Mohamed Y El-Naggar","doi":"10.1021/acsbiomaterials.4c01183","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01183","url":null,"abstract":"<p><p>Electroactive microorganisms such as <i>Geobacter sulfurreducens</i> can couple organic electron donor oxidation to the respiration of electrode surfaces, colonizing them in the process. These microbes can also reduce soluble metal ions, such as soluble Pd, resulting in metallic nanoparticle (NP) synthesis. Such NPs are valuable catalysts for industrially relevant chemical production; however, their chemical and solid-state syntheses are often energy-intensive and result in hazardous byproducts. Utilizing electroactive microbes for precious metal NP synthesis has the advantage of operating under more sustainable conditions. By combining <i>G. sulfurreducens</i>'s ability to colonize electrodes and synthesize NPs, we performed electrode cultivation ahead of biogenic Pd NP synthesis for the self-assembled fabrication of a cell-Pd biomaterial. <i>G. sulfurreducens</i> biofilms were grown in electrochemical reactors with added soluble Pd, and electrochemistry, spectroscopy, and electron microscopy were used to confirm (1) metabolic current production before and after Pd addition, (2) simultaneous electrode respiration and soluble Pd reduction over time, and (3) biofilm-localized Pd NP synthesis. Utilizing electroactive microbes for the controlled synthesis of NPs can enable the self-assembly of novel cell-nanoparticle biomaterials with unique electron transport and catalytic properties.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}