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  • 1.

    【2hr】Microphysiological systems

    包量

    机译 微生理系统
    摘要：
  • 2.

    【2hr】Disease-directed engineering for physiology-driven treatment interventions in neurological disorders

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    机译 疾病导向的神经疾病中生理驱动治疗干预的工程
    摘要：Neurological disease is killing us. While there have long been attempts to develop therapies for both acute and chronic neurological diseases, no current treatments are curative. Additionally, therapeutic development for neurological disease takes 15 years and often costs several billion dollars. More than 96% of these therapies will fail in late stage clinical trials. Engineering novel treatment interventions for neurological disease can improve outcomes and quality of life for millions; however, therapeutics should be designed with the underlying physiology and pathology in mind. In this perspective, we aim to unpack the importance of, and need to understand, the physiology of neurological disease. We first dive into the normal physiological considerations that should guide experimental design, and then assess the pathophysiological factors of acute and chronic neurological disease that should direct treatment design. We provide an analysis of a nanobased therapeutic intervention that proved successful in translation due to incorporation of physiology at all stages of the research process. We also provide an opinion on the importance of keeping a high-level view to designing and administering treatment interventions. Finally, we close with an implementation strategy for applying a disease-directed engineering approach. Our assessment encourages embracing the complexity of neurological disease, as well as increasing efforts to provide system-level thinking in our development of therapeutics for neurological disease.
  • 3.

    【2hr】The rationale and emergence of electroconductive biomaterial scaffolds in cardiac tissue engineering

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    机译 心脏组织工程中导电生物材料支架的基本原理和出现
    摘要：The human heart possesses minimal regenerative potential, which can often lead to chronic heart failure following myocardial infarction. Despite the successes of assistive support devices and pharmacological therapies, only a whole heart transplantation can sufficiently address heart failure. Engineered scaffolds, implantable patches, and injectable hydrogels are among the most promising solutions to restore cardiac function and coax regeneration; however, current biomaterials have yet to achieve ideal tissue regeneration and adequate integration due a mismatch of material physicochemical properties. Conductive fillers such as graphene, carbon nanotubes, metallic nanoparticles, and MXenes and conjugated polymers such as polyaniline, polypyrrole, and poly(3,4-ethylendioxythiophene) can possibly achieve optimal electrical conductivities for cardiac applications with appropriate suitability for tissue engineering approaches. Many studies have focused on the use of these materials in multiple fields, with promising effects on the regeneration of electrically active biological tissues such as orthopedic, neural, and cardiac tissue. In this review, we critically discuss the role of heart electrophysiology and the rationale toward the use of electroconductive biomaterials for cardiac tissue engineering. We present the emerging applications of these smart materials to create supportive platforms and discuss the crucial role that electrical stimulation has been shown to exert in maturation of cardiac progenitor cells.
  • 4.

    【2hr】Microfluidics-based skin irritation test using in vitro 3D angiogenesis platform

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    机译 使用体外3D血管生成平台的基于微流体的皮肤刺激性测试
    摘要：A global ban on animal experiments has been proposed. Hence, it is imperative to develop alternative models. Artificial skin models should reflect the responses of subcutaneous blood vessels and the immune system to elucidate disease and identify cosmetics' base materials. Notably, in vivo skin-irritation cascades involve disruption of the epidermal barrier and the release of proinflammatory mediators in response to chemical stimuli. Such proinflammatory factors promote angiogenesis and blood vessel permeability, as observed in irritant contact dermatitis. As an alternative to animal models, we propose a novel skin-irritation model based on a three-dimensional in vitro angiogenesis platform, in which irritated keratinocytes biochemically stimulate vascular endothelial growth factors. Our microfluidic platform hosts interactions between keratinocytes and dermal fibroblasts, which promote angiogenic sprouting. We use sodium lauryl sulfate (SLS) and steartrimonium chloride (SC) as chemical irritants. The irritative effects of SLS and SC are of particular interest due to the ubiquity of both SLS and SC in cosmetics. SLS was observed to significantly affect angiogenic performance, with increasing sprout length. Further promotion of vessel sprouting and lumen formation was observed with 10, 20, and 60 μM of SC, despite its classification as nonirritating and use in supposedly safe formulations. This platform provides an alternative to animal testing as a basis for testing cosmetics and pharmaceutical substances, in addition to serving as a disease model for irritant contact dermatitis.
  • 5.

    【2hr】Balance of interstitial flow magnitude and vascular endothelial growth factor concentration modulates three-dimensional microvascular network formation

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    机译 间隙流量大小和血管内皮生长因子浓度的平衡调节三维微血管网络的形成
    摘要：Hemodynamic and biochemical factors play important roles in critical steps of angiogenesis. In particular, interstitial flow has attracted attention as an important hemodynamic factor controlling the angiogenic process. Here, we applied a wide range of interstitial flow magnitudes to an in vitro three-dimensional (3D) angiogenesis model in a microfluidic device. This study aimed to investigate the effect of interstitial flow magnitude in combination with the vascular endothelial growth factor (VEGF) concentration on 3D microvascular network formation. Human umbilical vein endothelial cells (HUVECs) were cultured in a series of interstitial flow generated by 2, 8, and 25 mmH2O. Our findings indicated that interstitial flow significantly enhanced vascular sprout formation, network extension, and the development of branching networks in a magnitude-dependent manner. Furthermore, we demonstrated that the proangiogenic effect of interstitial flow application could not be substituted by the increased VEGF concentration. In addition, we found that HUVECs near vascular sprouts significantly elongated in >8 mmH2O conditions, while activation of Src was detected even in 2 mmH2O conditions. Our results suggest that the balance between the interstitial flow magnitude and the VEGF concentration plays an important role in the regulation of 3D microvascular network formation in vitro.
  • 6.

    【2hr】A human in vitro platform for the evaluation of pharmacology strategies in cardiac ischemia

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    机译 用于评估心肌缺血药理学策略的人类体外平台
    摘要：Cardiac ischemic events increase the risk for arrhythmia, heart attack, heart failure, and death and are the leading mortality condition globally. Reperfusion therapy is the first line of treatment for this condition, and although it significantly reduces mortality, cardiac ischemia remains a significant threat. New therapeutic strategies are under investigation to improve the ischemia survival rate; however, the current preclinical models to validate these fail to predict the human outcome. We report the development of a functional human cardiac in vitro system for the study of conduction velocity under ischemic conditions. The system is a bioMEMs platform formed by human iPSC derived cardiomyocytes patterned on microelectrode arrays and maintained in serum-free conditions. Electrical activity changes of conduction velocity, beat frequency, and QT interval (the QT-interval measures the period from onset of depolarization to the completion of repolarization) or action potential length can be evaluated over time and under the stress of ischemia. The optimized protocol induces >80% reduction in conduction velocity, after a 4 h depletion period, and a partial recovery after 72 h of oxygen and nutrient reintroduction. The sensitivity of the platform for pharmacological interventions was challenged with a gap junction modulator (ZP1609), known to prevent or delay the depression of conduction velocity induced by ischemic metabolic stress. ZP1609 significantly improved the drastic drop in conduction velocity and enabled a greater recovery. This model represents a new preclinical platform for studying cardiac ischemia with human cells, which does not rely on biomarker analysis and has the potential for screening novel cardioprotective drugs with readouts that are closer to the measured clinical parameters.
  • 7.

    【2hr】GSVD- and tensor GSVD-uncovered patterns of DNA copy-number alterations predict adenocarcinomas survival in general and in response to platinum

    包量

    机译 DNA拷贝数变化的GSVD和张量GSVD未发现模式可预测腺癌的总体生存以及对铂的反应
    摘要：More than a quarter of lung, uterine, and ovarian adenocarcinoma (LUAD, USEC, and OV) tumors are resistant to platinum drugs. Only recently and only in OV, patterns of copy-number alterations that predict survival in response to platinum were discovered, and only by using the tensor GSVD to compare Agilent microarray platform-matched profiles of patient-matched normal and primary tumor DNA. Here, we use the GSVD to compare whole-genome sequencing (WGS) and Affymetrix microarray profiles of patient-matched normal and primary LUAD, USEC, and OV tumor DNA. First, the GSVD uncovers patterns similar to one Agilent OV pattern, where a loss of most of the chromosome arm 6p combined with a gain of 12p encode for transformation. Like the Agilent OV pattern, the WGS LUAD and Affymetrix LUAD, USEC, and OV patterns are correlated with shorter survival, in general and in response to platinum. Like the tensor GSVD, the GSVD separates these tumor-exclusive genotypes from experimental inconsistencies. Second, by identifying the shorter survival phenotypes among the WGS- and Affymetrix-profiled tumors, the Agilent pattern proves to be a technology-independent predictor of survival, independent also of the best other indicator at diagnosis, i.e., stage. Third, like no other indicator, the pattern predicts the overall survival of OV patients experiencing progression-free survival, in general and in response to platinum. We conclude that comparative spectral decompositions, such as the GSVD and tensor GSVD, underlie a mathematically universal description of the relationships between a primary tumor's genotype and a patient's overall survival phenotype, which other methods miss.
  • 8.

    【2hr】Automated sensing and splitting of stem cell colonies on microraft arrays

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    机译 在微筏阵列上自动检测和分裂干细胞集落
    摘要：Human induced pluripotent stem cells (hiPSCs) are widely used for disease modeling, tissue engineering, and clinical applications. Although the development of new disease-relevant or customized hiPSC lines is of high importance, current automated hiPSC isolation technologies rely largely on the fluorescent labeling of cells, thus limiting the cell line development from many applications. The objective of this research was to develop a platform for high-throughput hiPSC cytometry and splitting that utilized a label-free cell sensing approach. An image analysis pipeline utilizing background subtraction and standard deviation projections was implemented to detect hiPSC colonies from bright-field microscopy data. The pipeline was incorporated into an automated microscopy system coupling quad microraft cell-isolation arrays, computer-based vision, and algorithms for smart decision making and cell sorting. The pipeline exhibited a hiPSC detection specificity of 98% and a sensitivity of 88%, allowing for the successful tracking of growth for hundreds of microcolonies over 7 days. The automated platform split 170 mother colonies from a microarray within 80 min, and the harvested daughter biopsies were expanded into viable hiPSC colonies suitable for downstream assays, such as polymerase chain reaction (PCR) or continued culture. Transmitted light microscopy offers an alternative, label-free modality for isolating hiPSCs, yet its low contrast and specificity for adherent cells remain a challenge for automation. This novel approach to label-free sensing and microcolony subsampling with the preservation of the mother colony holds the potential for hiPSC colony screening based on a wide range of properties including those measurable only by a cell destructive assay.
  • 9.

    【2hr】Varying solvent type modulates collagen coating and stem cell mechanotransduction on hydrogel substrates

    包量

    机译 多种溶剂类型可调节水凝胶基质上的胶原蛋白涂层和干细胞机械转导
    摘要：Type I collagen is the most abundant extracellular matrix protein in the human body and is commonly used as a biochemical ligand for hydrogel substrates to support cell adhesion in mechanotransduction studies. Previous protocols for conjugating collagen I have used different solvents; yet, how varying solvent pH and composition impacts the efficiency and distribution of these collagen I coatings remains unknown. Here, we examine the effect of varying solvent pH and type on the efficiency and distribution of collagen I coatings on polyacrylamide hydrogels. We further evaluate the effects of varying solvent on mechanotransduction of human mesenchymal stem cells (MSCs) by characterizing cell spreading and localization of Yes-Associated Protein (YAP), a key transcriptional regulator of mechanotransduction. Increasing solvent pH to 5.2 and above increased the heterogeneity of coating with collagen bundle formation. Collagen I coating highly depends on the solvent type, with acetic acid leading to the highest conjugation efficiency and most homogeneous coating. Compared to HEPES or phosphate-buffered saline buffer, acetic acid-dissolved collagen I coatings substantially enhance MSC adhesion and spreading on both glass and polyacrylamide hydrogel substrates. When acetic acid was used for collagen coatings, even the low collagen concentration (1 μg/ml) induced robust MSC spreading and nuclear YAP localization on both soft (3 kPa) and stiff (38 kPa) substrates. Depending on the solvent type, stiffness-dependent nuclear YAP translocation occurs at a different collagen concentration. Together, the results from this study validate the solvent type as an important parameter to consider when using collagen I as the biochemical ligand to support cell adhesion.
  • 10.

    【2hr】Bioengineering adult human heart tissue: How close are we?

    包量

    机译 生物工程成人心脏组织：我们离我们有多近？
    摘要：Human pluripotent stem cells (hPSCs) have extensive applications in fundamental biology, regenerative medicine, disease modelling, and drug discovery/toxicology. Whilst large numbers of cardiomyocytes can be generated from hPSCs, extensive characterization has revealed that they have immature cardiac properties. This has raised potential concerns over their usefulness for many applications and has led to the pursuit of driving maturation of hPSC-cardiomyocytes. Currently, the best approach for driving maturity is the use of tissue engineering to generate highly functional three-dimensional heart tissue. Although we have made significant progress in this area, we have still not generated heart tissue that fully recapitulates all the properties of an adult heart. Deciphering the processes driving cardiomyocyte maturation will be instrumental in uncovering the mechanisms that govern optimal heart function and identifying new therapeutic targets for heart disease.
  • 11.

    【2hr】Modeling cardiac complexity: Advancements in myocardial models and analyticaltechniques for physiological investigation and therapeutic development invitro

    包量

    机译 心脏复杂性建模：心肌模型和分析的进展生理学研究和治疗发展的技术体外
    摘要：Cardiomyopathies, heart failure, and arrhythmias or conduction blockages impact millions of patients worldwide and are associated with marked increases in sudden cardiac death, decline in the quality of life, and the induction of secondary pathologies. These pathologies stem from dysfunction in the contractile or conductive properties of the cardiomyocyte, which as a result is a focus of fundamental investigation, drug discovery and therapeutic development, and tissue engineering. All of these foci require in vitro myocardial models and experimental techniques to probe the physiological functions of the cardiomyocyte. In this review, we provide a detailed exploration of different cell models, disease modeling strategies, and tissue constructs used from basic to translational research. Furthermore, we highlight recent advancements in imaging, electrophysiology, metabolic measurements, and mechanical and contractile characterization modalities that are advancing our understanding of cardiomyocyte physiology. With this review, we aim to both provide a biological framework for engineers contributing to the field and demonstrate the technical basis and limitations underlying physiological measurement modalities for biologists attempting to take advantage of these state-of-the-art techniques.
  • 12.

    【2hr】Nanostructured carriers as innovative tools for cancer diagnosis and therapy

    包量

    机译 纳米结构载体是癌症诊断和治疗的创新工具
    摘要：Cancer accounts for millions of deaths every year and, due to the increase and aging of the world population, the number of new diagnosed cases is continuously rising. Although many progresses in early diagnosis and innovative therapeutic protocols have been already set in clinical practice, still a lot of critical aspects need to be addressed in order to efficiently treat cancer and to reduce several drawbacks caused by conventional therapies. Nanomedicine has emerged as a very promising approach to support both early diagnosis and effective therapy of tumors, and a plethora of different inorganic and organic multifunctional nanomaterials have been ad hoc designed to meet the constant demand for new solutions in cancer treatment. Given their unique features and extreme versatility, nanocarriers represent an innovative and easily adaptable tool both for imaging and targeted therapy purposes, in order to improve the specific delivery of drugs administered to cancer patients. The current review reports an in-depth analysis of the most recent research studies aiming at developing both inorganic and organic materials for nanomedical applications in cancer diagnosis and therapy. A detailed overview of different approaches currently undergoing clinical trials or already approved in clinical practice is provided.
  • 13.

    【2hr】Challenges and opportunities in exosome research—Perspectives from biology, engineering, and cancer therapy

    包量

    机译 外泌体研究的挑战与机遇-来自生物学，工程学和癌症治疗的观点
    摘要：Exosomes are small (∼30–140 nm) lipid bilayer-enclosed particles of endosomal origin. They are a subset of extracellular vesicles (EVs) that are secreted by most cell types. There has been growing interest in exosome research in the last decade due to their emerging role as intercellular messengers and their potential in disease diagnosis. Indeed, exosomes contain proteins, lipids, and RNAs that are specific to their cell origin and could deliver cargo to both nearby and distant cells. As a result, investigation of exosome cargo contents could offer opportunities for disease detection and treatment. Moreover, exosomes have been explored as natural drug delivery vehicles since they can travel safely in extracellular fluids and deliver cargo to destined cells with high specificity and efficiency. Despite significant efforts made in this relatively new field of research, progress has been held back by challenges such as inefficient separation methods, difficulties in characterization, and lack of specific biomarkers. In this review, we summarize the current knowledge in exosome biogenesis, their roles in disease progression, and therapeutic applications and opportunities in bioengineering. Furthermore, we highlight the established and emerging technological developments in exosome isolation and characterization. We aim to consider critical challenges in exosome research and provide directions for future studies.
  • 14.

    【2hr】Tunable synthetic extracellular matrices to investigate breast cancer response to biophysical and biochemical cues

    包量

    机译 可调节的合成细胞外基质，用于研究乳腺癌对生物物理和生化线索的反应
    摘要：The extracellular matrix (ECM) is thought to play a critical role in the progression of breast cancer. In this work, we have designed a photopolymerizable, biomimetic synthetic matrix for the controlled, 3D culture of breast cancer cells and, in combination with imaging and bioinformatics tools, utilized this system to investigate the breast cancer cell response to different matrix cues. Specifically, hydrogel-based matrices of different densities and modified with receptor-binding peptides derived from ECM proteins [fibronectin/vitronectin (RGDS), collagen (GFOGER), and laminin (IKVAV)] were synthesized to mimic key aspects of the ECM of different soft tissue sites. To assess the breast cancer cell response, the morphology and growth of breast cancer cells (MDA-MB-231 and T47D) were monitored in three dimensions over time, and differences in their transcriptome were assayed using next generation sequencing. We observed increased growth in response to GFOGER and RGDS, whether individually or in combination with IKVAV, where binding of integrin β1 was key. Importantly, in matrices with GFOGER, increased growth was observed with increasing matrix density for MDA-MB-231s. Further, transcriptomic analyses revealed increased gene expression and enrichment of biological processes associated with cell-matrix interactions, proliferation, and motility in matrices rich in GFOGER relative to IKVAV. In sum, a new approach for investigating breast cancer cell-matrix interactions was established with insights into how microenvironments rich in collagen promote breast cancer growth, a hallmark of disease progression in vivo, with opportunities for future investigations that harness the multidimensional property control afforded by this photopolymerizable system.
  • 15.

    【2hr】Modulation of adhesion microenvironment using mesh substrates triggers self-organization and primordial germ cell-like differentiation in mouse ES cells

    包量

    机译 使用网状基质调节粘附微环境触发小鼠ES细胞的自组织和原始生殖细胞样分化
    摘要：The cell adhesion microenvironment plays contributory roles in the induction of self-organized tissue formation and differentiation of pluripotent stem cells (PSCs). However, physical factors emanating from the adhesion microenvironment have been less investigated largely in part due to overreliance on biochemical approaches utilizing cytokines to drive in vitro developmental processes. Here, we report that a mesh culture technique can potentially induce mouse embryonic stem cells (mESCs) to self-organize and differentiate into cells expressing key signatures of primordial germ cells (PGCs) even with pluripotency maintained in the culture medium. Intriguingly, mESCs cultured on mesh substrates consisting of thin (5 μm-wide) strands and considerably large (200 μm-wide) openings which were set suspended in order to minimize the cell-substrate adhesion area, self-organized into cell sheets relying solely on cell-cell interactions to fill the large mesh openings by Day 2, and further into dome-shaped features around Day 6. Characterization using microarray analysis and immunofluorescence microscopy revealed that sheet-forming cells exhibited differential gene expressions related to PGCs as early as Day 2, but not other lineages such as epiblast, primitive endoderm, and trophectoderm, implying that the initial interaction with the mesh microenvironment and subsequent self-organization into cells sheets might have triggered PGC-like differentiation to occur differently from the previously reported pathway via epiblast-like differentiation. Overall, considering that the observed differentiation occurred without addition of known biochemical inducers, this study highlights that bioengineering techniques for modulating the adhesion microenvironment alone can be harnessed to coax PSCs to self-organize and differentiate, in this case, to a PGC-like state.
  • 16.

    【2hr】Matrix crosslinking enhances macrophage adhesion, migration, and inflammatory activation

    包量

    机译 基质交联可增强巨噬细胞的粘附，迁移和炎症激活
    摘要：Macrophages are versatile cells of the innate immune system that can adopt a variety of functional phenotypes depending on signals in their environment. In previous work, we found that culture of macrophages on fibrin, the provisional extracellular matrix protein, inhibits their inflammatory activation when compared to cells cultured on polystyrene surfaces. Here, we sought to investigate the role of matrix stiffness in the regulation of macrophage activity by manipulating the mechanical properties of fibrin. We utilize a photo-initiated crosslinking method to introduce dityrosine crosslinks to a fibrin gel and confirm an increase in gel stiffness through active microrheology. We observe that matrix crosslinking elicits distinct changes in macrophage morphology, integrin expression, migration, and inflammatory activation. Macrophages cultured on a stiffer substrate exhibit greater cell spreading and expression of αM integrin. Furthermore, macrophages cultured on crosslinked fibrin exhibit increased motility. Finally, culture of macrophages on photo-crosslinked fibrin enhances their inflammatory activation compared to unmodified fibrin, suggesting that matrix crosslinking regulates the functional activation of macrophages. These findings provide insight into how the physical properties of the extracellular matrix might control macrophage behavior during inflammation and wound healing.
  • 17.

    【2hr】Divide and conquer: A perspective on biochips for single-cell andrare-molecule analysis by next-generation sequencing

    包量

    机译 分而治之：单细胞和生物芯片的前景通过下一代测序进行稀有分子分析
    摘要：Recent advances in biochip technologies that connect next-generation sequencing (NGS) to real-world problems have facilitated breakthroughs in science and medicine. Because biochip technologies are themselves used in sequencing technologies, the main strengths of biochips lie in their scalability and throughput. Through the advantages of biochips, NGS has facilitated groundbreaking scientific discoveries and technical breakthroughs in medicine. However, all current NGS platforms require nucleic acids to be prepared in a certain range of concentrations, making it difficult to analyze biological systems of interest. In particular, many of the most interesting questions in biology and medicine, including single-cell and rare-molecule analysis, require strategic preparation of biological samples in order to be answered. Answering these questions is important because each cell is different and exists in a complex biological system. Therefore, biochip platforms for single-cell or rare-molecule analyses by NGS, which allow convenient preparation of nucleic acids from biological systems, have been developed. Utilizing the advantages of miniaturizing reaction volumes of biological samples, biochip technologies have been applied to diverse fields, from single-cell analysis to liquid biopsy. From this perspective, here, we first review current state-of-the-art biochip technologies, divided into two broad categories: microfluidic- and micromanipulation-based methods. Then, weprovide insights into how future biochip systems will aid some of the most importantbiological and medical applications that require NGS. Based on current and future biochiptechnologies, we envision that NGS will come ever closer to solving more real-worldscientific and medical problems.
  • 18.

    【2hr】Strategies for using mathematical modeling approaches to design and interpret multi-organ microphysiological systems (MPS)

    包量

    机译 使用数学建模方法设计和解释多器官微生理系统（MPS）的策略
    摘要：Recent advances in organ-on-a-chip technology have resulted in numerous examples of microscale systems that faithfully mimic the physiology and pathology of human organs and diseases. The next step in this field, which has already been partially demonstrated at a proof-of-concept level, would be integration of organ modules to construct multiorgan microphysiological systems (MPSs). In particular, there is interest in “body-on-a-chip” models, which recapitulate complex and dynamic interactions between different organs. Integration of multiple organ modules, while faithfully reflecting human physiology in a quantitative sense, will require careful consideration of factors such as relative organ sizes, blood flow rates, cell numbers, and ratios of cell types. The use of a mathematical modeling platform will be an essential element in designing multiorgan MPSs and interpretation of experimental results. Also, extrapolation to in vivo will require robust mathematical modeling techniques. So far, several scaling methods and pharmacokinetic and physiologically based pharmacokinetic models have been applied to multiorgan MPSs, with each method being suitable to a subset of different objectives. Here, we summarize current mathematical methodologies used for the design and interpretation of multiorgan MPSs and suggest important considerations and approaches to allow multiorgan MPSs to recapitulate human physiology and disease progression better, as well as help in vitro to in vivo translation of studies on response to drugs or chemicals.
  • 19.

    【2hr】Protein diffusion from microwells with contrasting hydrogel domains

    包量

    机译 蛋白质从具有相反水凝胶结构域的微孔中扩散
    摘要：Understanding and controlling molecular transport in hydrogel materials is important for biomedical tools, including engineered tissues and drug delivery, as well as life sciences tools for single-cell analysis. Here, we scrutinize the ability of microwells—micromolded in hydrogel slabs—to compartmentalize lysate from single cells. We consider both (i) microwells that are “open” to a large fluid (i.e., liquid) reservoir and (ii) microwells that are “closed,” having been capped with either a slab of high-density polyacrylamide gel or an impermeable glass slide. We use numerical modeling to gain insight into the sensitivity of time-dependent protein concentration distributions on hydrogel partition and protein diffusion coefficients and open and closed microwell configurations. We are primarily concerned with diffusion-driven protein loss from the microwell cavity. Even for closed microwells, confocal fluorescence microscopy reports that a fluid (i.e., liquid) film forms between the hydrogel slabs (median thickness of 1.7 μm). Proteins diffuse from the microwells and into the fluid (i.e., liquid) layer, yet concentration distributions are sensitive to the lid layer partition coefficients and the protein diffusion coefficient. The application of a glass lid or a dense hydrogel retains protein in the microwell, increasing the protein solute concentration in the microwell by ∼7-fold for the first 15 s. Using triggered release of Protein G from microparticles, we validate our simulations by characterizing protein diffusion in a microwell capped with a high-density polyacrylamide gel lid (p > 0.05, Kolmogorov-Smirnov test). Here, we establish and validate a numerical model useful for understanding protein transport in and losses from a hydrogel microwell across a range of boundary conditions.
  • 20.

    【2hr】Bactericidal activity of 3D-printed hydrogel dressing loaded with gallium maltolate

    包量

    机译 负载麦芽酚镓的3D打印水凝胶敷料的杀菌活性
    摘要：Chronic wounds are projected to reach epidemic proportions worldwide because of the aging population and the increasing incidence of diabetes. Despite extensive research, infection remains one of the leading sources of complications in chronic wounds, resulting in improper healing, biofilm formation, and lower extremity amputation. To address the limitations of standard treatments, we have developed a hydrogel wound dressing with self-tuning moisture control that incorporates a novel antimicrobial agent to eliminate and prevent infection. 3D-printing of a hydrogel dressing with dual porosity resulted in a new dressing with greater flexibility, increased water uptake, and more rapid swelling than bulk hydrogel dressings. Additionally, gallium maltolate (GaM) was incorporated into the dressing to investigate the efficacy of this antimicrobial agent. Loading profiles, release kinetics, and the bactericidal activity against Staphylococcus aureus (including methicillin-resistant Staphylococcus aureus) of GaM were investigated in vitro to identify target profiles that supported infection control. Finally, GaM-loaded hydrogel dressings were evaluated in vivo, utilizing a murine splinted-wound model that was inoculated with S. aureus. In comparison to an untreated control, GaM dressings markedly reduced the wound bacterial load without compromising wound closure rates. Overall, this work demonstrates the utility of a 3D-printed hydrogel dressing as an antimicrobial dressing to control infection in chronic wounds.
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