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Octopus -inspired gelatin-methacrylate scaffolds loaded with hBMSC-derived exosomes promote wound healing by regulating macrophage polarization 章鱼启发明胶-甲基丙烯酸酯支架装载hbmscs衍生的外泌体通过调节巨噬细胞极化促进伤口愈合
Q1 Engineering Pub Date : 2023-07-28 DOI: 10.1016/j.smaim.2023.07.002
Dong Yan , Guoqi Cao , Shumei Mao , Zehan Shang , Chengde Li , Guangdong Zhou , Xinping Li , Huitang Xia , Yibing Wang

Excessive local movement and inflammation are common problems in the process of wound repair, which lead to failure of later repair. In order to solve this problem, inspired by the octopus sucker structure, we successfully developed a photocrosslinked hydrogel that can adsorb skin surface fascia. In addition, extracellular vesicles from human bone marrow mesenchymal stem cells are encapsulated in the octopus like sucker structure. The morphology and structure of extracellular vesicles in bone marrow mesenchymal stem cells were detected by scanning electron microscopy and particle size analysis. Through iTRAQ, we tested the expression of angiogenesis related proteins contained in extracellular vesicles. Design small interfering RNA to verify its impact on angiogenic related genes and proteins. Macrophage polarization was detected by immunofluorescence. The expression of new blood vessels was detected by constructing a skin defect model and injecting microfil contrast agent into the heart. When the sucker is firmly adsorbed on the damaged wound, the sucker will slowly degrade. Using its delivery system, it is observed that the extracellular vesicles are released in the wound. Through iTRAQ, it was found that the angiogenesis regulator (angiopoietin-like 4, angiopoietin-like 3 and aminopeptidase N) released in the extracellular vesicles regulates collagen deposition, angiogenesis, and inhibits macrophage aggregation. In addition, the slowly released extracellular vesicles will further inhibit the polarization of proinflammatory macrophages. This biological behavior can provide an adaptive microenvironment for skin regeneration at an early stage. This new bionic octopus sucker structure gel creates a good microenvironment for wound repair and shortens the wound healing time. Therefore, this hydrogel inspired by the octopus sucker structure may provide a good strategy and commercial value for promoting wound repair treatment in clinical practice.

局部过度运动和炎症是创面修复过程中常见的问题,导致后期修复失败。为了解决这一问题,受章鱼吸盘结构的启发,我们成功开发了一种可以吸附皮肤表面筋膜的光交联水凝胶。此外,人骨髓间充质干细胞的胞外囊泡被包裹在章鱼状吸盘结构中。采用扫描电镜和粒度分析方法对骨髓间充质干细胞细胞外囊泡的形态和结构进行了观察。通过iTRAQ检测细胞外囊泡中血管生成相关蛋白的表达。设计小干扰RNA,验证其对血管生成相关基因和蛋白的影响。免疫荧光法检测巨噬细胞极化。通过建立皮肤缺损模型并注入微膜造影剂检测新生血管的表达。当吸盘牢固地吸附在受损伤口上时,吸盘就会慢慢降解。利用其输送系统,观察到细胞外囊泡在伤口中被释放。通过iTRAQ发现细胞外囊泡释放的血管生成调节剂(血管生成素样4、血管生成素样3和氨基肽酶N)调节胶原沉积、血管生成,抑制巨噬细胞聚集。此外,缓慢释放的细胞外囊泡会进一步抑制促炎巨噬细胞的极化。这种生物学行为可以为早期皮肤再生提供适应性微环境。这种新型仿生章鱼吸盘结构凝胶为伤口修复创造了良好的微环境,缩短了伤口愈合时间。因此,这种受章鱼吸盘结构启发的水凝胶可能在临床实践中为促进伤口修复治疗提供良好的策略和商业价值。
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引用次数: 2
Recent advances in three-dimensional printing in cardiovascular devices: Bench and bedside applications 心血管设备三维打印的最新进展:实验和床边应用
Q1 Engineering Pub Date : 2023-07-17 DOI: 10.1016/j.smaim.2023.07.001
Yihong Shen , Jie Cui , Xiao Yu , Jiahui Song , Pengfei Cai , Wanxin Guo , Yue Zhao , Jinglei Wu , Hongbing Gu , Binbin Sun , Xiumei Mo

Three-dimensional (3D) printing is emerging as an innovative technology, which is widely used in cardiovascular disease at bench and bedside. During the last decade, with the development of 3D printing industry, many 3D printed models have been used in clinic, because it can provide the advantage of haptic feedback, direct manipulation, and enhanced doctors’ understanding of cardiovascular anatomy and underlying pathologies. In addition to the preparation of 3D printed models, 3D printing technology also shows great application potential in cardiovascular regenerative medicine because it has the advantages of integrating cells, cytokines and materials. Although cardiovascular regenerative medicine application still has a gap between bench and bedside, this gap is gradually narrowing with the development of new materials and new technology of 3D printing recently. In this review, we firstly analyze the characteristics and clinical needs of cardiovascular diseases, and introduce the concept and category of 3D printing technology. Secondly, we summarize the application of 3D printed models, stents, vascular graft, vascular network, and heart organs at bench and bedside. In the end, we discuss the challenges and future perspectives of 3D printing in cardiovascular diseases.

三维(3D)打印是一项新兴的创新技术,广泛应用于心血管疾病的临床和临床。近十年来,随着3D打印行业的发展,许多3D打印模型已经应用于临床,因为它可以提供触觉反馈,直接操作,以及增强医生对心血管解剖和潜在病理的了解。除了3D打印模型的制备,3D打印技术在心血管再生医学方面也显示出巨大的应用潜力,因为它具有整合细胞、细胞因子和材料的优势。虽然心血管再生医学的应用在实验台和床边之间还存在差距,但随着近年来新材料和3D打印新技术的发展,这一差距正在逐渐缩小。本文首先分析了心血管疾病的特点和临床需求,介绍了3D打印技术的概念和分类。其次,总结了3D打印模型、支架、血管移植、血管网、心脏器官在临床和床边的应用。最后,我们讨论了3D打印在心血管疾病中的挑战和未来前景。
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引用次数: 2
Magnetosurgery: Principles, design, and applications 磁外科:原理、设计和应用
Q1 Engineering Pub Date : 2023-07-07 DOI: 10.1016/j.smaim.2023.06.008
Daniil V. Kladko, Vladimir V. Vinogradov

Magnetosurgery, the guidance or actuation of surgical instruments during operations using magnetic forces, has become a global trend in minimally invasive surgeries performed remotely. Despite the promise of the magnetosurgery platform, only select surgeries are compatible with this technology, and issues related to the engineering, materials used, and applications are still not fully understood. In this review, we focus on the engineering and material basis of magnetosurgery in order to summarize and expand existing knowledge to create a versatile platform with multiple surgical applications.

磁力手术,即在手术过程中利用磁力引导或驱动手术器械,已成为远程微创手术的全球趋势。尽管磁手术平台很有前景,但只有部分手术与该技术兼容,而且与工程、使用的材料和应用相关的问题仍未完全了解。在这篇综述中,我们着眼于磁外科的工程和材料基础,以总结和扩展现有的知识,以创建一个具有多种外科应用的通用平台。
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引用次数: 1
Bioactive carbon dots for tissue engineering applications 组织工程应用的生物活性炭点
Q1 Engineering Pub Date : 2023-06-23 DOI: 10.1016/j.smaim.2023.06.006
Qi Zong , Haolin Chen , Yi Zhao , Jinming Wang , Jun Wu

Carbon dots (CDs) are carbon-based zero-dimensional nanomaterials with characteristic sizes of less than 10 ​nm. Recently, bioactive CDs have made remarkable achievements in wound healing, bone and cartilage repair, neural regeneration, and myocardium regeneration owing to their unique physicochemical properties and excellent biocompatibility, which have significantly promoted the advancement of tissue engineering. Herein, we summarize the applications of bioactive CDs in tissue engineering. First, we briefly introduce the characteristics and synthesis methods of bioactive CDs. Subsequently, we review the applications of bioactive CDs in wound healing, bone and cartilage tissue engineering, neural tissue engineering, and cardiac tissue engineering in detail. Finally, we discuss the challenges and prospects of bioactive CDs in tissue engineering.

碳点(CD)是基于碳的零维纳米材料,其特征尺寸小于10​nm。近年来,生物活性CDs因其独特的理化性质和优异的生物相容性,在创伤愈合、骨软骨修复、神经再生和心肌再生等方面取得了显著成就,极大地推动了组织工程的发展。在此,我们总结了生物活性CDs在组织工程中的应用。首先,我们简要介绍了生物活性CDs的特性和合成方法。随后,我们详细综述了生物活性CD在创伤愈合、骨软骨组织工程、神经组织工程和心脏组织工程中的应用。最后,我们讨论了生物活性CD在组织工程中的挑战和前景。
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引用次数: 0
Real-time actuation of a dielectric elastomer actuator neuroprosthesis for facial paralysis 介电弹性体致动器神经假体用于面瘫的实时驱动
Q1 Engineering Pub Date : 2023-06-21 DOI: 10.1016/j.smaim.2023.06.003
Stefania Konstantinidi , Carlotta Imholz , Thomas Martinez , Amine Benouhiba , Armando Walter , Yoan Civet , Nicole Lindenblatt , Yves Perriard

Facial paralysis is a highly burdening condition, resulting in a patient's inability to move his mimic musculature on one or both sides of his face. This condition compromises the patient's communication and facial expressions, and thus dramatically reduces his quality of life. The current treatment for chronic facial paralysis relies on a complex reconstructive surgery. This publication proposes a novel, less invasive approach for dynamic facial reanimation. The use of a smart material, namely a Dielectric Elastomer Actuator (DEA) is proposed for facial motion restoration, thus avoiding the traditional two-stage free muscle transfer procedure and allowing for a faster recovery of the patient. DEAs are a type of electroactive polymers, showing promising properties similar to natural muscles such as the fact that they are soft, lightweight and allow for large displacements. As a result, a study of the facial muscles and neural interfaces, notably the ones responsible for mouth movement, was performed, in order to implement a realistic setup. In this paper, a non-invasive neural interface based on myoelectric signal is used in order to establish a real-time control of the actuator. Visible motion of a skin model is produced in real time, by synchronizing the actuator to the activity of a healthy muscle, with a maximal delay of 108 ​ms resulting from the signal processing and a delay of less than 30 ​ms related to the actuation of the DEA. This shows that the usage of DEA combined with a neural interface presents a promising approach for treatment of facial paralysis.

面瘫是一种负担很重的疾病,导致患者无法移动面部一侧或两侧的模拟肌肉组织。这种情况损害了患者的沟通和面部表情,从而大大降低了他的生活质量。目前慢性面瘫的治疗依赖于复杂的重建手术。该出版物提出了一种新颖的、侵入性较小的动态面部复活方法。建议使用智能材料,即介电弹性体致动器(DEA)进行面部运动恢复,从而避免了传统的两阶段自由肌肉转移程序,并允许患者更快地恢复。DEAs是一种电活性聚合物,显示出类似于天然肌肉的良好性能,例如它们柔软、重量轻,可以进行大位移。因此,为了实现逼真的设置,对面部肌肉和神经界面进行了研究,尤其是负责口腔运动的肌肉和神经接口。本文采用了一种基于肌电信号的无创神经接口来建立对执行器的实时控制。皮肤模型的可见运动是通过使致动器与健康肌肉的活动同步而实时产生的,最大延迟为108​ms,并且延迟小于30​ms与缉毒局的启动有关。这表明DEA与神经接口相结合的使用为治疗面瘫提供了一种很有前途的方法。
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引用次数: 0
Antibacterial silk sericin/poly (vinyl alcohol) hydrogel with antifungal property for potential infected large burn wound healing: Systemic evaluation 抗菌丝胶/聚乙烯醇水凝胶具有抗真菌性能,用于潜在感染的大面积烧伤创面愈合:系统评价
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2022.07.002
Bianza Moise Bakadia , Lallepak Lamboni , Abeer Ahmed Qaed Ahmed , Ruizhu Zheng , Biaou Oscar Ode Boni , Zhijun Shi , Shuyao Song , Tiatou Souho , Biampata Mutu Mukole , Fuyu Qi , Guang Yang

Hydrogel-based burn wound dressings with excellent antibacterial, antifungal, and mechanical properties are ideal biomaterials to promote infected large burn wound healing. In this study, the hydrogel synthesized by repetitive freezing-thawing consists of poly (vinyl alcohol) (PVA), silk sericin (SS), and azithromycin (AZM), with genipin (GNP) as crosslinker. The FTIR showed that all hydrogel components were successfully blended. The swelling ratio, porosity, cell attachment, and proliferation improved with SS incorporation, while increased PVA content enhanced the mechanical performance of the hydrogel. The inclusion of AZM improved the antimicrobial property of the hydrogel towards Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The hydrogel showed sustained SS and AZM releases as well as cytocompatibility on keratinocytes and fibroblasts. Furthermore, the hydrogel displays skin adhesion ability when freeze-dried. In the in vivo study using an infected mouse full-thickness burn model with a 10% total body surface area, it was shown that burn injury led to increased inflammatory cytokine responses and macroscopic and microscopic alterations in the spleen and liver. The kidneys, on the other hand, revealed neither change. Interestingly, the prepared hydrogel had a better burn wound healing effect than the commercial Tegaderm™ film dressing, minimizing systemic burn effects. Hence, this novel hydrogel is projected to be a promising candidate for accelerated healing of infected burn wounds.

水凝胶型烧伤创面敷料具有良好的抗菌、抗真菌和力学性能,是促进大面积感染烧伤创面愈合的理想生物材料。本研究以吉尼平(GNP)为交联剂,采用重复冻融法制备了聚乙烯醇(PVA)、丝胶蛋白(SS)和阿奇霉素(AZM)为主要原料的水凝胶。FTIR结果表明,所有水凝胶组分均成功混合。SS掺入提高了水凝胶的溶胀率、孔隙度、细胞附着和增殖,PVA含量的增加提高了水凝胶的力学性能。AZM的加入提高了水凝胶对金黄色葡萄球菌、铜绿假单胞菌、大肠杆菌和白色念珠菌的抗菌性能。水凝胶显示出持续的SS和AZM释放以及对角质形成细胞和成纤维细胞的细胞相容性。此外,水凝胶在冷冻干燥时表现出皮肤粘附能力。在体内研究中,使用感染的小鼠全层烧伤模型,其体表面积为10%,结果表明,烧伤损伤导致炎症细胞因子反应增加,脾脏和肝脏的宏观和微观改变。另一方面,肾脏没有显示出任何变化。有趣的是,制备的水凝胶比商业Tegaderm™膜敷料具有更好的烧伤创面愈合效果,最大限度地减少了全身烧伤影响。因此,这种新型水凝胶有望成为加速感染烧伤创面愈合的有希望的候选物。
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引用次数: 18
Immunomodulation-based development engineering for advancing metal soft tissue implants 基于免疫调节的金属软组织植入物开发工程
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.04.005
Shoucheng Chen , Jiamin Shi , Guangqi Gao , Lv Xie, Yingye Zhang, Zhengjie Shan, Zhuwei Huang, Xinchun Zhang, Zhuofan Chen, Zetao Chen

Metal materials have been widely applied clinically due to their superior mechanical properties. However, the integration of metallic implants with surrounding soft tissue remains challenging and may lead to severe infections and failure of treatments. Development of natural exemplar suggests that the establishment of the soft tissue integration around hard surfaces is a complex scenario associated with the coordination of epithelial tissue, connective tissue and immune cells. In addition, the influence of the peri-implant immune microenvironment on soft tissue integration reparative process has received increasing attention. Given that the properties of the metal implant could effectively modulate immune response, it is predictable to regulate the immune microenvironment around metal implants for optimized soft tissue integration. This review firstly compared the establishment of natural biological hard surface-soft tissue integration with metal implants, in which the important role of epithelial tissue, connective tissue and immune cells were emphasized. Furthermore, up-to-date research outcomes in the closely connections between the immune microenvironment and soft tissue integration were discussed and summarized. From the view of natural soft-hard tissue integration development and reparative process, the immunomodulation-based strategy is proposed to manipulate the immune microenvironment for the enhancement of soft tissue-metal implant integration.

金属材料因其优越的力学性能在临床上得到了广泛的应用。然而,金属植入物与周围软组织的整合仍然具有挑战性,可能导致严重的感染和治疗失败。自然样本的发展表明,硬表面周围软组织整合的建立是一个复杂的场景,与上皮组织、结缔组织和免疫细胞的协调有关。此外,种植体周围免疫微环境对软组织整合修复过程的影响也越来越受到关注。鉴于金属种植体的特性可以有效地调节免疫反应,调节金属种植体周围的免疫微环境以优化软组织整合是可以预见的。本文首先比较了天然生物硬表面-软组织整合体与金属植入体的建立,强调了上皮组织、结缔组织和免疫细胞在其中的重要作用。此外,对免疫微环境与软组织整合密切相关的最新研究成果进行了讨论和总结。从软硬组织的自然融合发展和修复过程出发,提出了基于免疫调节的策略来操纵免疫微环境以增强软组织-金属种植体的融合。
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引用次数: 1
Engineered multifunctional silk fibroin/gelatin hydrogel conduit loaded with miR-29a@ZIF-8 nanoparticles for peripheral nerve regeneration 负载miR-29a@ZIF-8纳米颗粒的工程多功能丝素/明胶水凝胶导管用于周围神经再生
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.02.002
Hao Wang , Hongxia Wan , Qiqi Wang , Ying Ma , Guorui Su , Xiaodong Cao , Huichang Gao

Peripheral nerve injury (PNI) is a common surgical disease. In recent years, with the development of tissue engineering materials, nerve guidance conduit (NGC) is expected to replace autologous nerve transplantation and become a new method for the treatment of PNI. In this work, we developed a multifunctional silk fibroin (SF)/gelatin-tyramine (GT) composite hydrogel conduit with flexible adjustable size by using a diffusion-driven cross-linking method. Furthermore, the ZIF-8 nanoparticles loaded with miR-29a (miR-29a@ZIF-8) delivery system was constructed and compounded into SF/GT hydrogel conduit to enhance its bioactivity and neural repair effects through sustained miR-29a release. In vitro cell experiments showed that SF/GT hydrogel conduit could significantly promote the myelination of Schwann cells (SCs), neuronal differentiation and axon extension of PC12 ​cells. In addition, it was worth mentioning that SF/GT hydrogel conduit could also regulate the immune microenvironment of nerve regeneration by promoting the transformation of macrophages from M1 phenotype to M2 phenotype, indicating a potential application as nerve guidance conduit in peripheral nerve repair.

周围神经损伤(PNI)是一种常见的外科疾病。近年来,随着组织工程材料的发展,神经引导管有望取代自体神经移植,成为治疗PNI的新方法。在本工作中,我们采用扩散驱动交联方法开发了一种尺寸可灵活调节的多功能丝素蛋白(SF)/明胶-酪胺(GT)复合水凝胶导管。此外,负载miR-29a的ZIF-8纳米颗粒(miR-29a@ZIF-8)构建了递送系统并将其复合到SF/GT水凝胶导管中,以通过持续释放miR-29a来增强其生物活性和神经修复效果。体外细胞实验表明,SF/GT水凝胶导管可显著促进许旺细胞(SC)的髓鞘形成、PC12的神经元分化和轴突延伸​细胞。此外,值得一提的是,SF/GT水凝胶导管还可以通过促进巨噬细胞从M1表型向M2表型的转化来调节神经再生的免疫微环境,表明其作为神经引导导管在外周神经修复中的潜在应用。
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引用次数: 2
Curcumin nano-prodrug induces multi-phase cell cycle arrest in colorectal cancer through suppression of CDKs and specific down-regulation of PLK1 姜黄素纳米前药通过抑制CDKs和特异性下调PLK1诱导结直肠癌多相细胞周期阻滞
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2023.06.001
Dong Xu , Xingzhi Feng , Yuxin Wan , Lanlan Yang , Qianling Gao , Zihuan Yang , Chang Du

Aberrant activation of cell cycle proteins leads to tumor progression in most cancer types. While 5-fluorouracil (5-Fu)-based chemotherapy remains the first-line treatment strategy for colorectal cancer (CRC), more than 40% of patients with advanced CRC do not benefit from the regimen. Herein, a chemically modified curcumin (mCur) was developed to explore its curative effect on CRC and reveal its potential role in cell cycle regulation. Amphiphilic mCur could self-assemble into positively charged nano-micelles, hence facilitating high cellular uptake and anticancer activity. Multi-phase cell cycle arrest, induced by both mCur and Cur, was first observed in HCT 116 ​cells. This phenomenon was mainly attributed to the Cur/mCur mediated downregulation of cyclin-dependent kinases (CDKs) and their direct interactions. Moreover, mCur and Cur treatments generated distinct phenotypic signatures. In particular, mCur induced distinct dynamic fluctuations in cell cycle and a relatively higher proportion of cells in the G2/M phase than Cur, and specifically triggered the impaired expression of polo-like kinase 1 (PLK1). An in vivo evaluation using a CRC patient-derived tumor xenograft (PDX) model indicated that mCur exhibited better antitumor effects via more significant downregulation of PLK1 in PLK1high PDX, with no obvious systemic toxicity. Collectively, our study revealed a unique multi-phase cell cycle arrest effect of Cur-based antitumor agents and highlighted the potential of mCur as a PLK1-targeted inhibitor for CRC therapy.

细胞周期蛋白的异常激活导致大多数癌症类型的肿瘤进展。虽然以5-氟尿嘧啶(5-Fu)为基础的化疗仍然是癌症(CRC)的一线治疗策略,但超过40%的晚期CRC患者没有从该方案中获益。本文开发了一种化学修饰的姜黄素(mCur),以探索其对CRC的疗效,并揭示其在细胞周期调控中的潜在作用。两亲性mCur可以自组装成带正电的纳米胶束,从而促进细胞的高摄取和抗癌活性。mCur和Cur诱导的多相细胞周期阻滞首次在HCT 116中观察到​细胞。这种现象主要归因于Cur/mCur介导的细胞周期蛋白依赖性激酶(CDKs)的下调及其直接相互作用。此外,mCur和Cur处理产生了不同的表型特征。特别是,mCur诱导了细胞周期的明显动态波动,G2/M期的细胞比例相对高于Cur,并特别触发了polo-like激酶1(PLK1)的表达受损。使用CRC患者来源的肿瘤异种移植物(PDX)模型进行的体内评估表明,mCur通过在PLK1高PDX中更显著地下调PLK1而表现出更好的抗肿瘤作用,没有明显的全身毒性。总之,我们的研究揭示了基于Cur的抗肿瘤药物独特的多期细胞周期阻滞作用,并强调了mCur作为PLK1靶向抑制剂用于CRC治疗的潜力。
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引用次数: 1
Erratum for previously published articles 以前发表的文章的勘误
Q1 Engineering Pub Date : 2023-01-01 DOI: 10.1016/j.smaim.2022.10.001
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引用次数: 0
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