Hydrogels

水凝胶
  • 文章类型: Journal Article
    水凝胶已成为再生医学中一类有前途的细胞外基质(ECM)模拟材料。这里,我们简要描述了当前的ECM模拟水凝胶的最新技术,从天然到混合到完全合成的版本,给出了超分子相互作用的重要性,使真正的ECM模拟的序幕。通过对两种不同的超分子水凝胶系统的关注,说明了超分子相互作用为细胞培养创建ECM模拟物的潜力。都是在我们的实验室开发的.我们用一些最近的,提出细胞-物质相互作用的重要设计原则的重要发现。为了实现细胞扩散,我们认为,缓慢的分子动力学(纤维内的单体交换)对于确保细胞粘附配体在超分子纤维内的稳固结合至关重要。缓慢的整体动力学(应力松弛--纤维重排,τ1/2≈1000s)是在软凝胶(<1kPa)中实现细胞扩散所必需的,而凝胶刚度超过了刚性凝胶中的动力学。重要的是,这与其他专门研究不同材料类型的研究结果相一致:如果底物松弛发生得比离合器结合和病灶粘附寿命更快,细胞扩散会受到损害。最后,我们讨论了超分子方法的考虑因素和局限性,并为进一步理解超分子水凝胶-细胞相互作用提供了前瞻性的思考视角。未来的工作可能会利用所提出的指导原则作为细胞-材料相互作用的基础,不仅可以实现下一代ECM模拟水凝胶,还可以推进其他领域。比如生物电子学,为创新应用开辟新的机遇。
    Hydrogels have emerged as a promising class of extracellular matrix (ECM)-mimicking materials in regenerative medicine. Here, we briefly describe current state-of-the-art of ECM-mimicking hydrogels, ranging from natural to hybrid to completely synthetic versions, giving the prelude to the importance of supramolecular interactions to make true ECM mimics. The potential of supramolecular interactions to create ECM mimics for cell culture is illustrated through a focus on two different supramolecular hydrogel systems, both developed in our laboratories. We use some recent, significant findings to present important design principles underlying the cell-material interaction. To achieve cell spreading, we propose that slow molecular dynamics (monomer exchange within fibers) is crucial to ensure the robust incorporation of cell adhesion ligands within supramolecular fibers. Slow bulk dynamics (stress-relaxation─fiber rearrangements, τ1/2 ≈ 1000 s) is required to achieve cell spreading in soft gels (<1 kPa), while gel stiffness overrules dynamics in stiffer gels. Importantly, this resonates with the findings of others which specialize in different material types: cell spreading is impaired in case substrate relaxation occurs faster than clutch binding and focal adhesion lifetime. We conclude with discussing considerations and limitations of the supramolecular approach as well as provide a forward thinking perspective to further understand supramolecular hydrogel-cell interactions. Future work may utilize the presented guidelines underlying cell-material interactions to not only arrive at the next generation of ECM-mimicking hydrogels but also advance other fields, such as bioelectronics, opening up new opportunities for innovative applications.
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  • 文章类型: Multicenter Study
    背景:钬激光前列腺摘除术(HoLEP)已成为治疗良性前列腺增生(BPH)的新黄金标准;然而,它陡峭的学习曲线阻碍了这种技术的推广。因此,需要一种台式HoLEP模拟器来减少这种学习曲线并提供训练。我们使用现代教育理论开发了一种非生物危险的HoLEP模拟器,并在多中心研究中对其进行了验证。
    方法:六位专家通过Delphi共识在三轮(包括250个问题)中为HoLEP模拟器建立了关键组件。在达成共识之后,数字设计是由专家创建和批准的,然后使用3D打印和水凝胶成型来制造物理原型。经过一个迭代的原型测试过程,专家们完成了一项调查,以五点李克特量表评估模拟器,以供最终批准。使用主观和客观绩效指标,在七个机构的56名专家和新手参与者中验证了批准的模型。
    结果:在85/250个问题上达成了共识,专家发现物理模型可以充分复制82.5%的所需特征。比较专家和新手的手术时间(37.4+/-8.2vs16.7+/-6.8分钟)时,客观指标具有统计学意义(p<0.0001),腺瘤重量(79.6+/-20.4vs36.2+/-9.9gm),和并发症(6vs22)。
    结论:我们成功完成了一项多中心研究,以通过现代教育理论开发和验证用于HoLEP的非生物危险台式模拟器。包括该模拟器在内的培训课程目前正在开发中。
    Background: Holmium laser enucleation of the prostate (HoLEP) has emerged as a new gold standard for treatment of benign prostatic hyperplasia; however, its steep learning curve hinders generalization of this technique. Therefore, there is a need for a benchtop HoLEP simulator to reduce this learning curve and provide training. We have developed a nonbiohazardous HoLEP simulator using modern education theory and validated it in a multicenter study. Materials and Methods: Six experts established key components for a HoLEP simulator through a Delphi consensus over three rounds including 250 questions. After consensus, a digital design was created and approved by experts, then used to fabricate a physical prototype using three-dimensional printing and hydrogel molding. After a process of iterative prototype testing, experts completed a survey assessing the simulator with a 5-point Likert scale for final approval. The approved model was validated with 56 expert and novice participants at seven institutions using subjective and objective performance metrics. Results: Consensus was reached on 85 of 250 questions, and experts found the physical model to adequately replicate 82.5% of required features. Objective metrics were statistically significant (p < 0.0001) when comparing experts and novices for enucleation time (37.4 ± 8.2 vs 16.7 ± 6.8 minutes), adenoma weight (79.6 ± 20.4 vs 36.2 ± 9.9 g), and complications (6 vs 22), respectively. Conclusion: We have effectively completed a multicenter study to develop and validate a nonbiohazardous benchtop simulator for HoLEP through modern education theory. A training curriculum including this simulator is currently under development.
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  • 文章类型: Practice Guideline
    肥胖的药物管理可改善预后并降低肥胖相关并发症的风险。该美国胃肠病学协会指南旨在支持从业人员做出有关超重和肥胖的药物干预措施的决定。
    由内容专家和指南方法学家组成的多学科小组使用了建议评估的分级,开发和评估框架,以优先考虑临床问题,确定以患者为中心的结果,并对以下药物进行证据合成:司马鲁肽2.4毫克,利拉鲁肽3.0mg,苯丁胺-托吡酯缓释(ER),纳曲酮-安非他酮,奥利司他,芬特明,二乙基丙酸,和Gelesis100口服超吸收水凝胶。指南小组使用证据决策框架来制定肥胖的药理学管理建议,并为临床实践提供实施考虑因素。
    指南小组提出了9条建议。专家组强烈建议对超重和肥胖(体重指数≥30kg/m2或体重相关并发症≥27kg/m2)的成年人对生活方式干预反应不足的成年人,除生活方式干预外,还应使用药物治疗。小组建议使用司马鲁肽2.4毫克,利拉鲁肽3.0mg,苯丁胺-托吡酯ER,和纳曲酮-安非他酮ER(基于中等确定性证据),和苯丁胺和二乙基丙酸(基于低确定性证据),用于超重和肥胖的长期管理。指南小组建议不要使用奥利司他。小组确定了使用Gelesis100口服超吸收水凝胶作为知识空白。
    在超重和肥胖的成年人中,仅对生活方式干预反应不足,建议长期药物治疗,具有多种有效和安全的治疗选择。
    Pharmacological management of obesity improves outcomes and decreases the risk of obesity-related complications. This American Gastroenterological Association guideline is intended to support practitioners in decisions about pharmacological interventions for overweight and obesity.
    A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis of the following agents: semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate extended-release (ER), naltrexone-bupropion ER, orlistat, phentermine, diethylpropion, and Gelesis100 oral superabsorbent hydrogel. The guideline panel used the evidence-to-decision framework to develop recommendations for the pharmacological management of obesity and provided implementation considerations for clinical practice.
    The guideline panel made 9 recommendations. The panel strongly recommended the use of pharmacotherapy in addition to lifestyle intervention in adults with overweight and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with weight-related complications) who have an inadequate response to lifestyle interventions. The panel suggested the use of semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER (based on moderate certainty evidence), and phentermine and diethylpropion (based on low certainty evidence), for long-term management of overweight and obesity. The guideline panel suggested against the use of orlistat. The panel identified the use of Gelesis100 oral superabsorbent hydrogel as a knowledge gap.
    In adults with overweight and obesity who have an inadequate response to lifestyle interventions alone, long-term pharmacological therapy is recommended, with multiple effective and safe treatment options.
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  • 文章类型: Journal Article
    在英国前列腺癌放射治疗期间,确定患者优先使用直肠水凝胶垫片的共识。
    德尔菲研究由两轮在线问卷组成,两次虚拟顾问委员会会议和一份最终的在线问卷。
    英国局部和局部晚期前列腺癌的根治性放射治疗。
    来自英国各地的六位领先的临床肿瘤学家和一位泌尿科医生。
    直肠水凝胶垫片。
    无报告。
    专家组就最小化具有治疗目的的治疗毒性的重要性达成共识,即使是低度毒性相关的不良事件也会显著影响生活质量。人们一致认为,尽管满足直肠剂量限制,太多的患者出现直肠毒性,符合条件的患者的直肠水凝胶间隔物显著减少了与毒性相关的不良事件.然而,由于资金的限制,患者需要优先使用垫片。在接受抗凝治疗的患者和患有糖尿病或炎症性肠病的患者中,可以预期间隔物的更高益处。但对于预期获益较少的患者群体未能达成共识.虽然放射治疗方案不是决定优先次序的主要因素,超分割方案有望获得更高的益处。
    有一个强烈和普遍的共识,即所有接受根治性放射治疗的前列腺癌患者都有可能从水凝胶间隔物中受益。目前,并非所有可能受益的患者都可以使用水凝胶垫片,访问是不平等的。实施共识建议可能有助于优先考虑和平衡英国患者对直肠间隔器的使用。
    To identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK.
    Delphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire.
    Radical radiation therapy for localised and locally advanced prostate cancer in the UK.
    Six leading clinical oncologists and one urologist from across the UK.
    Rectal hydrogel spacer.
    None reported.
    The panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens.
    There is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.
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  • 文章类型: Journal Article
    SARS-CoV-2的关注变体(VOC)的频繁出现需要一个灵敏且包罗万象的检测平台,尽管病毒突变,该平台仍然可行。在这种情况下,我们靶向所有VOC的糖蛋白(S蛋白)的受体结合域(RBD),并基于保守氨基酸构建了共有RBD(cRBD).然后,我们通过计算机模拟方法选择了对cRBD具有特异性的高亲和力ssDNA新型适体。选择的适体用于制造光子晶体(PC)装饰的aptasensor(APC传感器),它由聚丙烯酰胺水凝胶中聚合的聚苯乙烯纳米颗粒组成。cRBD响应的ssDNA适体在水凝胶网络中交联,选择性结合唾液样品中的cRBD和SARS-CoV-2。结合响应可以通过水凝胶的溶胀和通过来自PC的光的衍射的颜色产生来视觉监测,并且可以通过衍射环直径或光谱仪来定量。该传感器在唾液样本中,cRBD的LOD为12.7±0.55ngmL-1,SARS-CoV-2的LOD为3±18.8细胞mL-1,具有5分钟的快速反应。传感器可以在没有活性损失的情况下存储和再生。它可以用作SARS-CoV-2诊断的即时测试(POCT)。
    The frequent emergence of variants of concern (VOC) of SARS-CoV-2 necessitates a sensitive and all-inclusive detection platform that remains viable despite the virus mutations. In this context, we targeted the receptor-binding domain (RBD) of glycoprotein (S-protein) of all VOC and constructed a consensus RBD (cRBD) based on the conserved amino acids. Then, we selected a high-affinity ssDNA novel aptamer specific for the cRBD by an in silico approach. The selected aptamer is utilized to fabricate a photonic crystal (PC)-decorated aptasensor (APC-sensor), which consists of polystyrene nanoparticles polymerized within a polyacrylamide hydrogel. cRBD-responsive ssDNA aptamers are crosslinked in the hydrogel network, which selectively bind to the cRBD and SARS-CoV-2 in saliva samples. The binding response can be visually monitored by swelling of the hydrogel and color generation by diffraction of light from PCs and can be quantified by the diffraction ring diameter or a spectrometer. The sensor delivers a LOD of 12.7 ± 0.55 ng mL-1 for the cRBD and 3 ± 18.8 cells mL-1 for SARS-CoV-2 in saliva samples, with a rapid response of 5 min. The sensor can be stored and regenerated without loss of activity. It can be utilized as a point-of-care testing (POCT) for SARS-CoV-2 diagnosis.
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  • 文章类型: Journal Article
    Until the mid-1980s, mainly biologists were conducting peptide research. This changed with discoveries that opened new paths of research involving the use of peptides in bioengineering, biotechnology, biomedicine, nanotechnology, and bioelectronics. Peptide engineering and rational design of novel peptide sequences with unique and tailor-made properties further expanded the field. The discovery of short self-assembling peptides, which upon association form well-defined supramolecular architectures, created new and exciting areas of research. Depending on the amino acid sequence, the pH, and the type of the electrolyte in the medium, peptide self-assembly leads to the formation of nanofibers, which are further organized to form a hydrogel. In this review, the application of ionic complementary peptides which self-assemble to form nanofiber hydrogels for tissue engineering and regenerative medicine will be discussed through a selective presentation of the most important work performed during the last 25 years.
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  • 文章类型: English Abstract
    Currently there are no data reported in the literature supporting the recommendation for peri-urethral injections in first-line treatment. However, some authors emphasize that periurethral injection techniques can be used because of their good risk/benefit ratio in patients who are fragile, those who have already undergone surgery, and those who do not wish to have surgery. This option should be chosen based on efficacy, safety, and the patient\'s wishes. The product used should remain based on safety, ease of use, price, and the urologist\'s preferences. In all cases, efficacy decreases with time and repeated injections are often necessary to maintain a satisfactory result. The injectables are a possible first-line choice in very elderly patients and in those who do not wish to undergo surgery. After failure of surgical treatment and/or if there is sphincter deficiency, peri-urethral injections can be an alternative to a new surgery, but one must be aware that the results are clearly inferior to balloons or the sphincter. In cases where the urethra is attached due to previous interventions, peri-urethral injection is not indicated.
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  • 文章类型: Consensus Development Conference
    目的:就有助于卫生专业人员在日常实践中选择合适的伤口敷料的建议达成共识,因为系统评价仅发现有限的证据支持现代伤口敷料的报告适应症。
    方法:一个指导委员会从具有长期伤口护理经验的护理人员和医师(专家或全科医生)名单中选出了一个由27名没有声明利益冲突的专家组成的小组。这些名单是由15个法国学会提出的。
    方法:小组成员收到了最近的文献系统综述,由工作组确定的适应症分类,和敷料的定义。
    方法:指导委员会为两个小组中的每个小组设计了关于慢性伤口和急性伤口(包括烧伤)的问卷。共识方法来自RAND/UCLA采用的名义组技术。小组成员根据已发表的证据和他们自己的经验,对每种可能的敷料-适应症组合的相关性进行了评估。第一轮评级后,他们开会讨论结果并提出建议,然后参加第二轮评级。工作组同行审查了最终建议。
    结论:对于以下组合的使用达成了强烈共识:对于慢性伤口,(1)清创阶段,水凝胶;(2)造粒阶段,泡沫和低粘附性敷料;和(3)上皮形成阶段,水胶体和低粘附性敷料;对于急性伤口的上皮形成阶段,低依从性敷料。对于具体情况,以下敷料是有利的:脆弱的皮肤,低粘附性敷料;用于出血性伤口,藻酸盐;和恶臭伤口,活性炭。
    OBJECTIVE: To seek a consensus on recommendations that would help health professionals choose appropriate wound dressings in daily practice, since a systematic review found only limited evidence to support reported indications for modern wound dressings.
    METHODS: A steering committee selected a panel of 27 experts with no declared conflicts of interest from lists of nursing staff and physicians (specialists or general practitioners) with long-standing experience of wound care. The lists were put forward by 15 French learned societies.
    METHODS: The panelists received a recent systematic review of the literature, a classification of indications established by a working group, and definitions for the dressings.
    METHODS: The steering committee designed questionnaires on chronic wounds and on acute wounds including burns for each of the 2 panels. The consensus method was derived from the nominal group technique adapted by RAND/UCLA. Panelists rated the relevance of each possible dressing-indication combination on the basis of the published evidence and their own experience. After the first round of rating, they met to discuss results and propose recommendations before taking part in a second round of rating. The working group peer reviewed the final recommendations.
    CONCLUSIONS: A strong consensus was reached for use of the following combinations: for chronic wounds, (1) debridement stage, hydrogels; (2) granulation stage, foam and low-adherence dressings; and (3) epithelialization stage, hydrocolloid and low-adherence dressings; and for the epithelialization stage of acute wounds, low-adherence dressings. For specific situations, the following dressings were favored: for fragile skin, low-adherence dressings; for hemorrhagic wounds, alginates; and for malodorous wounds, activated charcoal.
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