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  • NLM标题： Bioeng Transl Med
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共147条结果
  • 1.

    【2hr】Multivariate learning framework for long‐term adaptation in the artificial pancreas

    包量

    机译 人工胰腺长期适应的多元学习框架
    摘要：The long‐term use of the artificial pancreas (AP) requires an automated insulin delivery algorithm that can learn and adapt with the growth, development, and lifestyle changes of patients. In this work, we introduce a data‐driven AP adaptation method for improved glucose management in a home environment. A two‐phase Bayesian optimization assisted parameter learning algorithm is proposed to adapt basal and carbohydrate‐ratio profile, and key feedback control parameters. The method is evaluated on the basis of the 111‐adult cohort of the FDA‐accepted UVA/Padova type 1 diabetes mellitus simulator through three scenarios with lifestyle disturbances and incorrect initial parameters. For all the scenarios, the proposed method is able to robustly adapt AP parameters for improved glycemic regulation performance in terms of percent time in the euglycemic range [70, 180] mg/dl without causing risk of hypoglycemia in terms of percent time below 70 mg/dl.
  • 2.

    【2hr】Method of establishing breast cancer brain metastases affects brain uptake and efficacy of targeted, therapeutic nanoparticles

    包量

    机译 建立乳腺癌脑转移的方法影响脑吸收和靶向治疗性纳米颗粒的功效
    摘要：HER2‐targeted therapies effectively control systemic disease, but their efficacy against brain metastases is hindered by their low penetration of the blood‐brain and blood‐tumor barriers (BBB and BTB). We investigate brain uptake and antitumor efficacy of transferrin receptor (TfR)‐targeted, therapeutic nanoparticles designed to transcytose the BBB/BTB in three murine models. Two known models involving intracranial (IC) or intracardiac (ICD) injection of human breast cancer cells were employed, as was a third model developed here involving intravenous (IV) injection of the cells to form whole‐body tumors that eventually metastasize to the brain. We show the method of establishing brain metastases significantly affects therapeutic BBB/BTB penetration. Free drug accumulates and delays growth in IC‐ and ICD‐formed brain tumors, while non‐targeted nanoparticles show uptake and inhibition only in IC‐established metastases. TfR‐targeted nanoparticles accumulate and significantly delay growth in all three models, suggesting the IV model maintains a more intact BBB/BTB than the other models.
  • 3.

    【2hr】Polymeric curcumin nanoparticles by a facile in situ method for macrophage targeted delivery

    包量

    机译 高分子姜黄素纳米粒子通过方便的原位方法用于巨噬细胞靶向输送
    摘要：Targeting macrophages is a promising strategy for improved therapy of intracellular infections as macrophages exhibit rapid phagocytosis of particles >200 nm. Entrapment of Curcumin (CUR) in nanocarriers could provide bioenhancement and macrophage targeting. We present a simple and facile in situ nanoprecipitation approach for instantaneous and on‐site generation of curcumin nanoparticles (ISCurNP). ISCurNP optimised by Box‐Behnken design exhibited average size of 208.25 ± 7.55 nm and entrapment efficiency of 90.16 ± 1.17%. Differential scanning calorimetry and X‐Ray diffraction confirmed amorphization of CUR in ISCurNP. Sustained release was observed over 72 hr in vitro at lysosomal pH 4.5. Rapid and high uptake in RAW 264.7 macrophages was confirmed by flow cytometry and high performance liquid chromatography. Confocal microscopy established localisation of ISCurNP in lysosomal compartment. The facile in situ nanoprecipitation method provides simple, scalable technology to enable macrophage targeted delivery of CUR, with great promise for improved therapy of intracellular infections.
  • 4.

    【2hr】Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

    包量

    机译 去细胞细胞外基质在骨软骨组织工程中的应用
    摘要：Regenerative therapies for bone and cartilage injuries are currently unable to replicate the complex microenvironment of native tissue. There are many tissue engineering approaches attempting to address this issue through the use of synthetic materials. Although synthetic materials can be modified to simulate the mechanical and biochemical properties of the cell microenvironment, they do not mimic in full the multitude of interactions that take place within tissue. Decellularized extracellular matrix (dECM) has been established as a biomaterial that preserves a tissue's native environment, promotes cell proliferation, and provides cues for cell differentiation. The potential of dECM as a therapeutic agent is rising, but there are many limitations of dECM restricting its use. This review discusses the recent progress in the utilization of bone and cartilage dECM through applications as scaffolds, particles, and supplementary factors in bone and cartilage tissue engineering.
  • 5.

    【2hr】Engineering, on‐demand manufacturing, and scaling‐up of polymeric nanocapsules

    包量

    机译 聚合物纳米胶囊的工程设计，按需生产和按比例放大
    摘要：Polymeric nanocapsules are versatile delivery systems with the capacity to load lipophilic drugs in their oily nucleus and hydrophilic drugs in their polymeric shell. The objective of this work was to expand the technological possibilities to prepare customized nanocapsules. First, we adapted the solvent displacement technique to modulate the particle size of the resulting nanocapsules in the 50–500 nm range. We also produced nanosystems with a shell made of one or multiple polymer layers i.e. chitosan, dextran sulphate, hyaluronate, chondroitin sulphate, and alginate. In addition, we identified the conditions to translate the process into a miniaturized high‐throughput tailor‐made fabrication that enables massive screening of formulations. Finally, the production of the nanocapsules was scaled‐up both in a batch production, and also using microfluidics. The versatility of the properties of these nanocapsules and their fabrication technologies is expected to propel their advance from bench to clinic.
  • 6.

    【2hr】Interpretation of the mechanism of action of antituberculosis drug bedaquiline based on a novel two‐ion theory of energy coupling in ATP synthesis

    包量

    机译 基于新的能量耦合两离子理论在ATP合成中抗结核药物苯达喹啉的作用机理解释
    • 作者：Sunil Nath
    • 刊名：Bioengineering Translational Medicine
    • 2019年第1期
    摘要：Tuberculosis (TB) claims the lives of 1.3 million people each year, more than any other bacterial infection. Hence great interest was generated in health communities upon the recent introduction of the new diarylquinoline anti‐TB drug, bedaquiline. Bedaquiline acts by binding to the c‐subunit in the membrane‐bound FO portion of the F1FO‐adenosine triphosphate (ATP) synthase, the universal enzyme that produces the ATP needed by cells. However, the mechanism of killing by bedaquiline is not fully understood. Recent observations related to the bactericidal effects of bedaquiline, which show that it is a potent uncoupler of respiration‐driven ATP synthesis in Mycobacterium smegmatis are summarized. These observations are then interpreted from the standpoint of Nath's two‐ion theory of energy coupling in ATP synthesis (Nath, Biophys. Chem. 2017; 230:45–52). Especial importance is given to the interpretation of biochemical fluorescence quenching data, and the differences between the uncoupling induced by bedaquiline from that by the classical anionic uncouplers of oxidative phosphorylation are highlighted. Suggestions for new experiments that could lead to a better understanding of the uncoupling mechanism are made. A model of uncoupling action by the drug is presented, and the biochemical basis underlying uncoupling of ATP synthesis and lethality in mycobacteria is elucidated. The major biological implications arising from these novel insights are discussed. It is hoped that the analysis will lead to a more fundamental understanding of biological energy coupling, uncoupling and transduction, and to an integrated view for the design of novel antimicrobials by future research in the field.
  • 7.

    【2hr】Rescuing mesenchymal stem cell regenerative properties on hydrogel substrates post serial expansion

    包量

    机译 连续扩增后在水凝胶基质上拯救间充质干细胞的再生特性
    摘要：The use of human mesenchymal stem/stromal cells (hMSCs) in most clinical trials requires millions of cells/kg, necessitating ex vivo expansion typically on stiff substrates (tissue culture polystyrene [TCPS]), which induces osteogenesis and replicative senescence. Here, we quantified how serial expansion on TCPS influences proliferation, expression of hMSC‐specific surface markers, mechanosensing, and secretome. Results show decreased proliferation and surface marker expression after five passages (P5) and decreased mechanosensing ability and cytokine production at later passages (P11‐P12). Next, we investigated the capacity of poly(ethylene glycol) hydrogel matrices (E ~ 1 kPa) to rescue hMSC regenerative properties. Hydrogels reversed the reduction in cell surface marker expression observed at P5 on TCPS and increased secretion of cytokines for P11 hMSCs. Collectively, these results show that TCPS expansion significantly changes functional properties of hMSCs. However, some changes can be rescued by using hydrogels, suggesting that tailoring material properties could improve in vitro expansion methods.
  • 8.

    【2hr】Biodegradable bioadhesive nanoparticle incorporation of broad‐spectrum organic sunscreen agents

    包量

    机译 结合了广谱有机防晒剂的可生物降解的生物粘合剂纳米颗粒
    摘要：Conventional emulsion‐based sunscreen formulations are limited by postapplication epicutaneous penetration that increases the risk of allergic dermatitis, cellular damage, and filter photodegradation upon ultraviolet radiation (UVR) exposure. Encapsulation of the UVB filter padimate O within bioadhesive biodegradable nanoparticles (BNPs) composed of poly(d,l‐lactic acid)‐hyperbranched polyglycerol was previously shown to enhance UVR protection while preventing skin absorption. Herein, we assess the capacity of BNP co‐incorporation of avobenzone and octocrylene to provide broad‐spectrum UVR protection. The ratio of UV filters within nanoparticles (NPs) was optimized for filter–filter stabilization upon UV irradiation and maximum drug loading. In vitro water‐resistance test showed significant particle retention at 85% over 3 hr. In a pilot clinical study, protection against UVR‐induced erythema of BNPs was found to be comparable to the FDA standard P2. Thus, sunscreen formulations utilizing BNP incorporation of a combination of organic filters may offer key safety and performance advantages.
  • 9.

    【2hr】Self‐healing encapsulation and controlled release of vaccine antigens from PLGA microparticles delivered by microneedle patches

    包量

    机译 通过微针贴片从PLGA微粒中自我修复封装并控制疫苗抗原的释放
    摘要：There is an urgent need to reduce reliance on hypodermic injections for many vaccines to increase vaccination safety and coverage. Alternative approaches include controlled release formulations, which reduce dosing frequencies, and utilizing alternative delivery devices such as microneedle patches (MNPs). This work explores development of controlled release microparticles made of poly (lactic‐ ‐glycolic acid) (PLGA) that stably encapsulate various antigens though aqueous active self‐healing encapsulation (ASE). These microparticles are incorporated into rapid‐dissolving MNPs for intradermal vaccination.
  • 10.

    【2hr】Issue Information – Table of Contents

    包量

    机译 发行信息–目录
    • 作者：
    • 刊名：Bioengineering Translational Medicine
    • 2018年第2期
    摘要：
  • 11.

    【2hr】Issue Information – Table of Contents

    包量

    机译 发行信息–目录
    • 作者：
    • 刊名：Bioengineering Translational Medicine
    • 2018年第1期
    摘要：
  • 12.

    【2hr】Engineering molecular imaging strategies for regenerative medicine

    包量

    机译 再生医学的工程分子成像策略
    摘要：The reshaping of the world's aging population has created an urgent need for therapies for chronic diseases. Regenerative medicine offers a ray of hope, and its complex solutions include material, cellular, or tissue systems. We review basics of regenerative medicine/stem cells and describe how the field of molecular imaging, which is based on quantitative, noninvasive, imaging of biological events in living subjects, can be applied to regenerative medicine in order to interrogate tissues in innovative, informative, and personalized ways. We consider aspects of regenerative medicine for which molecular imaging will benefit. Next, genetic and nanoparticle‐based cell imaging strategies are discussed in detail, with modalities like magnetic resonance imaging, optical imaging (near infra‐red, bioluminescence), raman microscopy, and photoacoustic microscopy), ultrasound, computed tomography, single‐photon computed tomography, and positron emission tomography. We conclude with a discussion of “next generation” molecular imaging strategies, including imaging host tissues prior to cell/tissue transplantation.
  • 13.

    【2hr】BioTM Buzz (Volume 3, Issue 3)

    包量

    机译 BioTM Buzz（第3卷，第3期）
    • 作者：Aaron C. Anselmo
    • 刊名：Bioengineering Translational Medicine
    • 2018年第3期
    摘要：
  • 14.

    【2hr】Engineering clinical translation‐Introduction to Special Issue Dedicated to 2017 Bioengineering and Translational Medicine Conference

    包量

    机译 工程临床翻译-2017年生物工程与转化医学会议专刊简介
    摘要：
  • 15.

    【2hr】Introduction to Editorial Board Member: Professor Kristi S. Anseth

    包量

    机译 编辑委员会成员简介：Kristi S. Anseth教授
    摘要：
  • 16.

    【2hr】Derivation of neural crest stem cells from human epidermal keratinocytes requires FGF‐2, IGF‐1, and inhibition of TGF‐β1

    包量

    机译 从人表皮角质形成细胞衍生神经rest干细胞需要FGF-2，IGF-1和抑制TGF-β1
    摘要：Neural crest (NC) cells play a central role in forming the peripheral nervous system, the craniofacial skeleton, and the pigmentation of the skin during development due to their broad multilineage differentiation potential into neurons, Schwann cells, melanocytes, and mesenchymal stem cells. Recently, we identified an easily accessible source of pluripotent NC stem cells from human inter‐follicular keratinocyte (KC) cultures (KC‐NC). In this work, we examined specific conditions for the derivation of NC from KC cultures. More specifically, we examined the role of two growth factors, FGF2 and IGF1, in NC proliferation and in expression of two potent NC transcription factors, Sox10 and FoxD3. Using specific chemical inhibitors, we uncovered that the downstream regulatory pathways AKT/PI3K, MEK/ERK, and JNK/cJun may be critical in Sox10 and FoxD3 regulation in KC‐NC. The TGF‐β1 pathway was also implicated in suppressing Sox10 expression and NC proliferation. In summary, our study shed light into the role of FGF2, IGF1, and TGF‐β1 on the induction of NC from KC cultures and the pathways that regulate Sox10 and FoxD3. We also established culture conditions for sustaining KC‐NC multipotency and, therefore, the potential of these cells for regenerative medicine and cellular therapies.
  • 17.

    【2hr】Encapsulation of mesenchymal stem cells in glycosaminoglycans‐chitosan polyelectrolyte microcapsules using electrospraying technique: Investigating capsule morphology and cell viability

    包量

    机译 使用电喷雾技术将间充质干细胞包裹在糖胺聚糖-壳聚糖聚电解质微胶囊中：研究胶囊的形态和细胞活力
    摘要：Polyelectrolyte microcapsules are modular constructs which facilitate cell handling and assembly of cell‐based tissue constructs. In this study, an electrospray (ES) encapsulation apparatus was developed for the encapsulation of mesenchymal stem cells (MSCs). Ionic complexation between glycosaminoglycans (GAGs) and chitosan formed a polyelectrolyte complex membrane at the interface. To optimize the capsules, the effect of voltage, needle size and GAG formulation on capsule size were investigated. It was observed that by increasing the voltage and decreasing the needle size, the capsule size would decrease but at voltages above 12 kV, capsule size distribution broadened significantly which yields lower circularity. Increase in GAG viscosity resulted in larger microcapsules and cell viability exhibited no significant changes during the encapsulation procedure. These results suggest that ES is a highly efficient, and scalable approach to the encapsulation of MSCs for subsequent use in bioprinting and other modular tissue engineering or regenerative medicine applications.
  • 18.

    【2hr】A platform of genetically engineered bacteria as vehicles for localized delivery of therapeutics: Toward applications for Crohn's disease

    包量

    机译 基因工程细菌作为平台，用于局部递送治疗药物：克罗恩病的应用
    摘要：For therapies targeting diseases of the gastrointestinal tract, we and others envision probiotic bacteria that synthesize and excrete biotherapeutics at disease sites. Toward this goal, we have engineered commensal E. coli that selectively synthesize and secrete a model biotherapeutic in the presence of nitric oxide (NO), an intestinal biomarker for Crohn's disease (CD). This is accomplished by co‐expressing the pore forming protein TolAIII with the biologic, granulocyte macrophage‐colony stimulating factor (GM‐CSF). We have additionally engineered these bacteria to accumulate at sites of elevated NO by engineering their motility circuits and controlling pseudotaxis. Importantly, because we have focused on in vitro test beds, motility and biotherapeutics production are spatiotemporally characterized. Together, the targeted recognition, synthesis, and biomolecule delivery comprises a “smart” probiotics platform that may have utility in the treatment of CD. Further, this platform could be modified to accommodate other pursuits by swapping the promoter and therapeutic gene to reflect other disease biomarkers and treatments, respectively.
  • 19.

    【2hr】Engineered E. coli Nissle 1917 for the reduction of vancomycin‐resistant Enterococcus in the intestinal tract

    包量

    机译 工程化的大肠杆菌Nissle 1917，用于减少肠道中耐万古霉素的肠球菌
    摘要：Vancomycin‐resistant Enterococcus (VRE) poses a serious threat in hospitals where they densely colonize the intestinal tracts of patients. In vulnerable hosts, these pathogens may translocate to the bloodstream and become lethal. The ability to selectively reduce VRE in the intestinal tracts of patients could potentially prevent many of these translocation events and reduce the spread of the pathogen. Herein, we have engineered Escherichia. coli Nissle 1917 to produce and secrete three antimicrobial peptides, Enterocin A, Enterocin B, and Hiracin JM79, to specifically target and kill Enterococcus. These peptides exhibited potent activity against both Enterococcus faecium and Enterococcus faecalis, the two most prominent species responsible for VRE infections. We first discuss the optimization of the system used to express and secrete the peptides. We then show that by simultaneously expressing these peptides, both E. faecium and E. faecalis were drastically inhibited. We then demonstrate a suppression of the development of resistance when supernatant from the E. coli producer strains was used to treat E. faecium. Finally, we tested the efficacy of the probiotic in a VRE colonization model in mice. These studies showed that administration of the engineered probiotic significantly reduced the levels of both E. faecium and E. faecalis in the feces of male Balb/cJ mice.
  • 20.

    【2hr】Hepatitis B vaccination using a dissolvable microneedle patch is immunogenic in mice and rhesus macaques

    包量

    机译 使用可溶解的微针贴片进行的乙型肝炎疫苗接种对小鼠和恒河猴都有免疫原性
    摘要：Chronic Hepatitis B virus infection remains a major global public health problem, accounting for about 887,000 deaths in 2015. Perinatal and early childhood infections are strongly associated with developing chronic hepatitis B. Adding a birth dose of the hepatitis B vaccine (HepB BD) to routine childhood vaccination can prevent over 85% of these infections. However, HepB BD coverage remains low in many global regions, with shortages of birth attendants trained to vaccinate and limited HepB BD supply at birth. To address the challenges, we developed coated metal microneedle patches (cMNPs) and dissolvable microneedle patches (dMNPs) that deliver adjuvant‐free hepatitis B vaccine to the skin in a simple‐to‐administer manner. The dMNP contains micron‐scale, solid needles encapsulating vaccine antigen and dissolve in the skin, generating no sharps waste. We delivered HepB BD via cMNP to BALB/c mice and via dMNP to both mice and rhesus macaques. Both cMNP and dMNP were immunogenic, generating hepatitis B surface antibody levels similar to human seroprotection. Biomechanical analysis showed that at high forces the microneedles failed mechanically by yielding but microneedles partially blunted by axial compression were still able to penetrate skin. Overall, this study indicates that with further development, dMNPs could offer a method of vaccination to increase HepB BD access and reduce needle waste in developing countries.
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