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147条结果
  • 机译 BioTM嗡嗡声
    • 作者:Aaron C. Anselmo
    • 刊名:Bioengineering Translational Medicine
    • 2017年第3期
    摘要:
  • 机译 微流体共培养设备,可评估纳米颗粒对癌细胞团的渗透
    摘要:In vitro and in vivo assessment of safety and efficacy are the essential first steps in developing nanoparticle‐based therapeutic systems. However, it is often challenging to use the knowledge gained from in vitro studies to predict the outcome of in vivo studies since the complexity of the in vivo environment, including the existence of flow and a multicellular environment, is often lacking in traditional in vitro models. Here, we describe a microfluidic co‐culture model comprising 4T1 breast cancer cells and EA.hy926 endothelial cells under physiological flow conditions and its utilization to assess the penetration of therapeutic nanoparticles from the vascular compartment into a cancerous cell mass. Camptothecin nanocrystals (∼310 nm in length), surface‐functionalized with PEG or folic acid, were used as a test nanocarrier. Camptothecin nanocrystals exhibited only superficial penetration into the cancerous cell mass under fluidic conditions, but exhibited cytotoxicity throughout the cancerous cell mass. This likely suggests that superficially penetrated nanocrystals dissolve at the periphery and lead to diffusion of molecular camptothecin deep into the cancerous cell mass. The results indicate the potential of microfluidic co‐culture devices to assess nanoparticle‐cancerous cell interactions, which are otherwise difficult to study using standard in vitro cultures.
  • 机译 可溶性VI胶原蛋白处理增强了间充质干细胞对工程软骨的扩增
    摘要:Bone Marrow‐derived mesenchymal stem cells (BM‐MSC) are an attractive source for cell‐based therapies in cartilage injury owing to their efficient differentiation into chondrocytes and their immune‐suppressive abilities. However, their clinical use is hampered by a scarcity of cells leading to compromised efficacy. While expansion of human MSC ex vivo can potentially overcome the scarcity of cells, current methods lead to a rapid loss of the stem cell properties. In this study, we report soluble Collagen VI (cartilage pericellular matrix component) as a potential biologic that can expand the MSC population while maintaining the stem cell phenotype as confirmed by expression of the stem cell markers CD105 and CD90. Short‐term treatment with Collagen VI additionally retains the potential of MSC to differentiate into mature chondrocytes in pellet culture. Cartilage pellets generated from MSC treated with Collagen VI or control express comparable amounts of the chondrogenic markers Collagen II, Aggrecan and Sox9, and the extracellular glycosaminoglycans. Our observations confirm that the use of the endogenous and cartilage‐specific factor Collagen VI is valuable for a rapid and efficient expansion of MSC for potential use in cartilage regeneration and osteoarthritis.
  • 机译 Wyss研究所:跨学术-工业界的医疗技术创新和翻译的新模式
    摘要:The Wyss Institute for Biologically Inspired Engineering at Harvard University was formed based on the recognition that breakthrough discoveries cannot change the world if they never leave the laboratory. The Institute's mission is to discover the biological principles that Nature uses to build living things, and to harness these insights to create biologically inspired engineering innovations to advance human health and create a more sustainable world. Since its launch in 2009, the Institute has developed a new model for innovation, collaboration, and technology translation within academia, breaking “silos” to enable collaborations that cross institutional and disciplinary barriers. Institute faculty and staff engage in high‐risk research that leads to transformative breakthroughs. The biological principles uncovered are harnessed to develop new engineering solutions for medicine and healthcare, as well as nonmedical areas, such as energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and the formation of new start‐ups that are driven by a unique internal business development team including entrepreneurs‐in‐residence with domain‐specific expertise. Here, we describe this novel organizational model that the Institute has developed to change the paradigm of how fundamental discovery, medical technology innovation, and commercial translation are carried out at the academic‐industrial interface.
  • 机译 特刊简介:2016年转化医学与生物工程会议
    摘要:
  • 机译 在心血管支架和封堵器中的翻译:从生物稳定到完全可降解
    摘要:Cardiovascular disease is a major cause of morbidity and mortality, especially in developed countries. Most academic research efforts in cardiovascular disease management focus on pharmacological interventions, or are concerned with discovering new disease markers for diagnosis and monitoring. Nonpharmacological interventions with therapeutic devices, conversely, are driven largely by novel materials and device design. Examples of such devices include coronary stents, heart valves, ventricular assist devices, and occluders for septal defects. Until recently, development of such devices remained largely with medical device companies. We trace the materials evolution story in two of these devices (stents and occluders), while also highlighting academic contributions, including our own, to the evolution story. Specifically, it addresses not only our successes, but also the challenges facing the translatability of concepts generated via academic research.
  • 机译 直接比较寡糖赤藓红素作为潜在的血液替代品
    摘要:While many blood substitutes are based on mammalian hemoglobins (e.g., human hemoglobin, HbA), the naturally extracellular hemoglobins of invertebrates (a.k.a. erythrocruorins, Ecs) are intriguing alternative oxygen carriers. Specifically, the erythrocruorin of Lumbricus terrestris has been shown to effectively deliver oxygen in mice and rats without the negative side effects observed with HbA. In this study, the properties of six oligochaete Ecs (Lumbricus terrestris, Eisenia hortensis, Eisenia fetida, Eisenia veneta, Eudrilus eugeniae, and Amynthas gracilis) were compared in vitro to identify the most promising blood substitute candidate(s). Several metrics were used to compare the Ecs, including their oxidation rates, dissociation at physiological pH, thermal stability, and oxygen transport characteristics. Overall, the Ecs of Lumbricus terrestris (LtEc) and Eisenia fetida (EfEc) were identified as promising candidates, since they demonstrated high thermal and oligomeric stability, while also exhibiting relatively low oxidation rates. Interestingly, the O2 affinity of LtEc (P 50 = 26.25 mmHg at 37 °C) was also observed to be uniquely lower than EfEc and all of the other Ecs (P 50 = 9.29–13.62 mmHg). Subsequent alignment of the primary sequences of LtEc and EfEc revealed several significant amino acid substitutions within the D subunit interfaces that may be responsible for this significant change in O2 affinity. Nonetheless, these results show that LtEc and EfEc are promising potential blood substitutes that are resistant to oxidation and denaturation, but additional experiments will need to be conducted to determine their safety, efficacy, and the effects of their disparate oxygen affinities in vivo.
  • 机译 BioTM嗡嗡声
    • 作者:Aaron C. Anselmo
    • 刊名:Bioengineering Translational Medicine
    • 2017年第2期
    摘要:
  • 机译 聚乙二醇二丙烯酸酯微针通过溶胀作用输送肽
    摘要:Transdermal delivery of therapeutic biomolecules (including peptides) can avoid enzymatic digestion that occurs in the oral route. (Polyethylene glycol) diacrylate (PEGDA)‐based microneedles, with good biocompatibility, are easily fabricated through photo‐polymerization with a precisely controlled structure. It has successfully been used for the transdermal delivery of small molecule drugs such as 5‐fluorouracil. However, the delivery of peptide‐based therapeutics using this platform is seldom reported. This is because of the potential damage to the peptide during the photo‐polymerization process of PEGDA. Herein, we introduce a method to load PEGDA microneedles with peptides without compromising peptide potency. Using gap junction inhibitor (Gap 26) as an example, the peptide was loaded into PEGDA microneedles through the swelling effect of PEGDA in the aqueous solution. The peptide‐loaded microneedles were applied to a keloid scar model and exhibited inhibition expression of collagen I, a predominant marker of keloid scar, demonstrating its potential therapeutic effects.
  • 机译 聚(2-丙基丙烯酸)/聚(乳酸-乙醇酸)共混微粒作为靶向抗原递送系统,指导CD4 +或CD8 + T细胞活化
    摘要:Poly(lactic‐co‐glycolic acid) (PLGA) based microparticles (MPs) are widely investigated for their ability to load a range of molecules with high efficiency, including antigenic proteins, and release them in a controlled manner. Micron‐sized PLGA MPs are readily phagocytosed by antigen presenting cells, and localized to endosomes. Due to low pH and digestive enzymes, encapsulated protein cargo is largely degraded and processed in endosomes for MHC‐II loading and presentation to CD4+ T cells, with very little antigen delivered into the cytosol, limiting MHC‐I antigenic loading and presentation to CD8+ T cells. In this work, PLGA was blended with poly(2‐propylacrylic acid) (PPAA), a membrane destabilizing polymer, in order to incorporate an endosomal escape strategy into PLGA MPs as an easily fabricated platform with diverse loading capabilities, as a means to enable antigen presentation to CD8+ T cells. Ovalbumin (OVA)‐loaded MPs were fabricated using a water‐in‐oil double emulsion with a 0% (PLGA only), 3 and 10% PPAA composition. MPs were subsequently determined to have an average diameter of 1 µm, with high loading and a release profile characteristic of PLGA. Bone marrow derived dendritic cells (DCs) were then incubated with MPs in order to evaluate localization, processing, and presentation of ovalbumin. Endosomal escape of OVA was observed only in DC groups treated with PPAA/PLGA blends, which promoted high levels of activation of CD8+ OVA‐specific OT‐I T cells, compared to DCs treated with OVA‐loaded PLGA MPs which were unable activate CD8+ T cells. In contrast, DCs treated with OVA‐loaded PLGA MPs promoted OVA‐specific OT‐II CD4+ T cell activation, whereas PPAA incorporation into the MP blend did not permit CD4+ T cell activation. These studies demonstrate PLGA MP blends containing PPAA are able to provide an endosomal escape strategy for encapsulated protein antigen, enabling the targeted delivery of antigen for tunable presentation and activation of either CD4+ or CD8+ T cells.
  • 机译 细胞培养参数对间充质干细胞来源的细胞外囊泡产生和血管化生物活性的影响
    摘要:Mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) have emerged as potential therapeutic agents for numerous applications. EVs offer potential advantages over cell‐based therapies with regard to safety, stability and clearance profiles, however production and potency limitations must be addressed to enable eventual translation of EV‐based approaches. Thus, we sought to examine the role of specific cell culture parameters on MSC EV production and bioactivity toward informing rational design parameters for scalable EV biomanufacturing. We report significantly reduced MSC EV vascularization bioactivity, as measured by an endothelial cell gap closure assay, with increasing passage in culture by trypsinization, especially beyond passage 4. We further show that increased frequency of EV collection yielded higher numbers of EVs from the same initial number of MSCs over a 24 hr period. Finally, we demonstrate that decreased cell seeding density in culture flasks resulted in increased production of EVs per cell in MSCs and other cell types. Overall, these studies highlight the need for careful consideration of the parameters of cell passage number and cell seeding density in the production of therapeutic EVs at laboratory scale and for rational design of large‐scale EV biomanufacturing schemes.
  • 机译 脱落的PEG水凝胶改善了由于外科手术骨架导致的动脉弹性降低
    摘要:Arteries for bypass grafting are harvested either with neighboring tissue attached or as skeletonized vessels that are free of surrounding tissue. There are significant benefits to skeletonization, but reports suggest that skeletonized vessels may develop structural defects and are at risk for atherosclerosis. We investigated the specific short‐term effects of skeletonization on carotid artery biomechanics and microanatomy in a rabbit model. Six carotid arteries were surgically skeletonized. To support healing, three of these received polyethylene glycol hydrogel injected along their exterior surfaces. M‐mode ultrasonography was used to track circumferential cyclic strain in the skeletonized, hydrogel‐treated, and contralateral vessels. On day 21, the arteries were harvested, and vessel structure was assessed by histology, immunofluorescence microscopy, two‐photon elastin autofluorescence, and second harmonic generation (SHG) microscopy. Intimal‐medial thickness appeared unaffected by skeletonization, but the SHG signals indicated significant changes in collagen turnover in the adventitia. Skeletonized arteries also exhibited significantly decreased radial compliance (circumferential cyclic strain dropped ∼30%) and decreased numbers of elastic laminae (9.1 ± 2.0 to 2.3 ± 1.4). Hydrogel treatment protected against these effects with treated vessels maintaining normal mechanical properties. These results indicate that arterial skeletonization triggers immediate effects on vessel remodeling and reduced vessel compliance resulting in specific tissue alterations within 21 days, but that these effects can be attenuated by the placement of hydrogel on the exterior surface of the skeletonized vessel.
  • 机译 人多能干细胞来源的心外膜祖细胞可以分化为心内膜样内皮细胞
    摘要:During heart development, epicardial progenitors contribute various cardiac lineages including smooth muscle cells, cardiac fibroblasts, and endothelial cells. However, their specific contribution to the human endothelium has not yet been resolved, at least in part due to the inability to expand and maintain human primary or pluripotent stem cell (hPSC)‐derived epicardial cells. Here we first generated CDH5‐2A‐eGFP knock‐in hPSC lines and differentiated them into self‐renewing WT1+ epicardial cells, which gave rise to endothelial cells upon VEGF treatment in vitro. In addition, we found that the percentage of endothelial cells correlated with WT1 expression in a WT1‐2A‐eGFP reporter line. The resulting endothelial cells displayed many endocardium‐like endothelial cell properties, including high expression levels of endocardial‐specific markers, nutrient transporters and well‐organized tight junctions. These findings suggest that human epicardial progenitors may have the capacity to form endocardial endothelium during development and have implications for heart regeneration and cardiac tissue engineering.
  • 机译 IgA和IgM蛋白主要驱动血浆中电晕诱导的PLGA纳米颗粒粘附减少
    摘要:The high abundance of immunoglobulins (Igs) in the plasma protein corona on poly(lactic‐co‐glycolic) acid (PLGA)‐based vascular‐targeted carriers (VTCs) has previously been shown to reduce their adhesion to activated endothelial cells (aECs) in human blood flow. However, the relative role of individual Ig classes (e.g., IgG, IgA, and IgM) in causing adhesion reduction remains largely unknown. Here, we characterized the influence of specific Ig classes in prescribing the binding efficiency of PLGA nano‐sized VTCs in blood flow. Specifically, we evaluated the flow adhesion to aECs of PLGA VTCs with systematic depletion of various Igs in their corona. Adhesion reduction was largely eliminated for PLGA VTCs when all Igs were removed from the corona. Furthermore, re‐addition of IgA or IgM to the Igs‐depleted corona reinstated the low adhesion of PLGA VTCs, as evidenced by ∼40–70% reduction relative to particles with an Igs‐deficient corona. However, re‐addition of a high concentration of IgG to the Igs‐depleted corona did not cause significant adhesion reduction. Overall, the presented results reveal that PLGA VTC adhesion reduction in blood flows is primarily driven by high adsorption of IgA and IgM in the particle corona. Pre‐coating of albumin on PLGA VTCs mitigated the extent of adhesion reduction in plasma for some donors but was largely ineffective in general. Overall, this work may shed light into effective control of protein corona composition, thereby enhancing VTC functionality in vivo for eventual clinical use.
  • 机译 排卵检测,当前可用方法综述
    摘要:The ability to identify the precise time of ovulation is important for women who want to plan conception or practice contraception. Here, we review the current literature on various methods for detecting ovulation including a review of point‐of‐care device technology. We incorporate an examination of methods to detect ovulation that have been developed and practiced for decades and analyze the indications and limitations of each—transvaginal ultrasonography, urinary luteinizing hormone detection, serum progesterone and urinary pregnanediol 3‐glucuronide detection, urinary follicular stimulating hormone detection, basal body temperature monitoring, and cervical mucus and salivary ferning analysis. Some point‐of‐care ovulation detection devices have been developed and commercialized based on these methods, however previous research was limited by small sample size and an inconsistent standard reference to true ovulation.
  • 机译 设计具有免疫调节特性的生物材料,用于组织工程和再生医学
    摘要:Recent research in the vaccine and immunotherapy fields has revealed that biomaterials have the ability to activate immune pathways, even in the absence of other immune‐stimulating signals. Intriguingly, new studies reveal these responses are influenced by the physicochemical properties of the material. Nearly all of this work has been done in the vaccine and immunotherapy fields, but there is tremendous opportunity to apply this same knowledge to tissue engineering and regenerative medicine. This review discusses recent findings that reveal how material properties—size, shape, chemical functionality—impact immune response, and links these changes to emerging opportunities in tissue engineering and regenerative medicine. We begin by discussing what has been learned from studies conducted in the contexts of vaccines and immunotherapies. Next, research is highlighted that elucidates the properties of materials that polarize innate immune cells, including macrophages and dendritic cells, toward either inflammatory or wound healing phenotypes. We also discuss recent studies demonstrating that scaffolds used in tissue engineering applications can influence cells of the adaptive immune system—B and T cell lymphocytes—to promote regenerative tissue microenvironments. Through greater study of the intrinsic immunogenic features of implantable materials and scaffolds, new translational opportunities will arise to better control tissue engineering and regenerative medicine applications.
  • 机译 mAb生产工艺的发展趋势
    摘要:Monoclonal antibodies (mAbs) have established themselves as the leading biopharmaceutical therapeutic modality. The establishment of robust manufacturing platforms are key for antibody drug discovery efforts to seamlessly translate into clinical and commercial successes. Several drivers are influencing the design of mAb manufacturing processes. The advent of biosimilars is driving a desire to achieve lower cost of goods and globalize biologics manufacturing. High titers are now routinely achieved for mAbs in mammalian cell culture. These drivers have resulted in significant evolution in process platform approaches. Additionally, several new trends in bioprocessing have arisen in keeping with these needs. These include the consideration of alternative expression systems, continuous biomanufacturing and non‐chromatographic separation formats. This paper discusses these drivers in the context of the kinds of changes they are driving in mAb production processes.
  • 机译 外来体在癌症治疗和诊断中的新兴应用
    摘要:Exosomes are nanoscale extracellular vesicles that are shed from different cells in the body. Exosomes encapsulate several biomolecules including lipids, proteins, and nucleic acids, and can therefore play a key role in cellular communication. These vesicles can be isolated from different body fluids and their small sizes make them attractive in various biomedical applications. Here, we review state‐of‐the art approaches in exosome isolation and purification, and describe their potential use in cancer vaccines, drug delivery, and diagnostics.
  • 机译 特刊简介:生物工程治疗学。下一代药物开发
    • 作者:Pankaj Karande
    • 刊名:Bioengineering Translational Medicine
    • 2017年第1期
    摘要:
  • 机译 BioTM嗡嗡声
    • 作者:Aaron Anselmo
    • 刊名:Bioengineering Translational Medicine
    • 2017年第1期
    摘要:

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