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Biomaterials based growth factor delivery for brain regeneration after injury 基于生物材料的生长因子输送用于损伤后脑再生
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2022.04.001
Zhen Xu , Siyu Liu , Min Liang , Haoyi Yang , Chunqi Chang

Brain injury often caused irreversible loss of neural tissue and resulted in serious neurological disability. Owing to the extreme complexity of the brain, it is still challenging to regenerate the brain tissue from injury and restore its normal function. Growth factors are critical signaling molecules that promote endogenous neural stem/progenitor cells (NSPCs) proliferation, migration and differentiation, resulting in functional brain recovery from injury. However, the labile nature of growth factor motivated us to develop advanced growth factor delivery strategies to precisely control over its release profile in vivo. In this review, we will discuss growth factor delivery via biomaterials for brain regeneration after injury. This review begins with an overview of some major forms of brain injury. The characteristic properties of growth factors are described to provide a biological basis for their use in the brain regeneration. The specific biomaterials that generally used for delivering growth factor to treat brain injury are also detailed summarized. In particular, we focus on an engineering strategy that promote endogenous repair by creating growth factor concentration gradients in vivo. The last part of the review introduces current challenges and perspectives for growth factor delivery via biomaterials.

脑损伤往往造成神经组织的不可逆损失,并导致严重的神经功能障碍。由于大脑的极端复杂性,使脑组织从损伤中再生并恢复其正常功能仍然具有挑战性。生长因子是促进内源性神经干/祖细胞(NSPCs)增殖、迁移和分化,导致脑功能损伤恢复的关键信号分子。然而,生长因子的不稳定性促使我们开发先进的生长因子递送策略,以精确控制其在体内的释放。在这篇综述中,我们将讨论通过生物材料递送生长因子用于损伤后的脑再生。这篇综述首先概述了一些主要形式的脑损伤。本文描述了生长因子的特性,为其在脑再生中的应用提供了生物学基础。并对目前用于输送生长因子治疗脑损伤的特定生物材料进行了详细的综述。我们特别关注一种通过在体内创造生长因子浓度梯度来促进内源性修复的工程策略。回顾的最后一部分介绍了当前的挑战和前景的生长因子输送通过生物材料。
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引用次数: 0
Localized delivery of FTY-720 from 3D printed cell-laden gelatin/silk fibroin composite scaffolds for enhanced vascularized bone regeneration 3D打印细胞明胶/丝素复合支架的FTY-720局部递送,增强血管化骨再生
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2022.01.007
Jin Yang , Changxu Deng , Muhammad Shafiq , Zhihui Li , Qianqian Zhang , Haibo Du , Shikai Li , Xiaojun Zhou , Chuanglong He

Three-dimensional (3D) printing can construct products with accurate complex architecture. Engineered bone tissues that can promote vascularization and regulate directed differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) are considered as an ideal substitute the healing of bone for bone defects treatment. Herein, we fabricated a 3D printed BMSCs-laden scaffold using methacrylated gelatin and methacrylated silk fibroin (GelMA/SFMA) based bioinks along with localized sustained release of a small molecule drug fingolimod (FTY-720) for the synergistic interactions of vascularization and osteogenesis during bone repair. The GelMA/SFMA bioink showed significant advantages due to their tunable rheology, rapid thermal crosslinking, and improved shape fidelity following bioprinting. The in vitro experiments demonstrated that high cell viability of cells-laden constructs, while FTY-720-containing scaffolds significantly promoted migration and induced tube-like structure formation of human umbilical vein endothelial cells (HUVECs) as well as expressed high osteogenic-related genes expression of BMSCs. The implantation in a critical-size rat cranial defect model further revealed that FTY-720-loaded scaffolds significantly promoted vascularization and bone regeneration. Furthermore, scaffolds carrying BMSCs and FTY-720 were more osteogenic in vivo than scaffolds carrying BMSCs alone. Therefore, the constructed BMSCs-laden and FTY-720-loaded GelMA/SFMA scaffolds would be an ideal candidate with required structure and desired function for vascularization of bone regeneration.

三维(3D)打印可以构建具有精确复杂结构的产品。工程骨组织能够促进血管化和调节骨髓间充质干细胞(BMSCs)的定向分化,被认为是骨愈合治疗骨缺损的理想替代品。在此,我们使用甲基丙烯酸明胶和甲基丙烯酸丝素(GelMA/SFMA)为基础的生物墨水,以及小分子药物fingolimod (FTY-720)的局部持续释放,制造了一个3D打印的bmscs负载支架,用于骨修复过程中血管化和成骨的协同相互作用。GelMA/SFMA生物链接具有显著的优势,因为它们具有可调的流变性、快速的热交联和生物打印后提高的形状保真度。体外实验表明,载细胞构建体具有较高的细胞活力,而含fty -720的支架可显著促进人脐静脉内皮细胞(HUVECs)的迁移和诱导管状结构的形成,并表达BMSCs的高成骨相关基因表达。在临界尺寸大鼠颅骨缺损模型中植入fty -720进一步表明,负载fty -720支架可显著促进血管形成和骨再生。此外,携带BMSCs和FTY-720的支架在体内比单独携带BMSCs的支架具有更强的成骨性。因此,构建的bmscs负载和fty -720负载的GelMA/SFMA支架将是具有骨再生血管化所需结构和功能的理想候选材料。
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引用次数: 15
Biodegradable Zn–Sr alloys with enhanced mechanical and biocompatibility for biomedical applications 可生物降解的Zn–Sr合金,具有增强的机械性能和生物相容性,用于生物医学应用
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2021.12.004
Yingchao Su , Jiayin Fu , Shaokang Du , Elias Georgas , Yi-Xian Qin , Yufeng Zheng , Yadong Wang , Donghui Zhu

Zinc (Zn) is a new generation of biodegradable metal as temporary biomedical implants with a promising degradation rate. However, its clinical applications have been limited because of the insufficient mechanical properties. Considering the degradation property and biocompatibility, we proposed Zn–Sr alloys after extrusion treatments to simultaneously improve the mechanical strength and ductility. The in vitro and in vivo degradation and biocompatibility were also evaluated using electrochemical and immersion corrosion tests, various cell and bacterial models, together with subcutaneous and femoral implantations in rats. Results showed that the extruded Zn-0.7Sr alloys exhibited two times higher mechanical strengths (∼120 ​MPa) and better ductility (∼10%) than the pure Zn counterparts. The Zn–Sr alloys provided enhanced in vitro and in vivo biocompatibility along with promising antibacterial properties.

锌(Zn)是新一代生物可降解金属,是一种具有良好降解性能的生物医用临时植入物。然而,由于其力学性能不足,其临床应用受到限制。考虑到锌锶合金的降解性能和生物相容性,我们提出了经过挤压处理的锌锶合金,以同时提高机械强度和塑性。通过电化学和浸没腐蚀试验、各种细胞和细菌模型以及大鼠皮下和股骨植入,评估了其体外和体内降解和生物相容性。结果表明,挤压Zn-0.7 sr合金的力学强度(~ 120mpa)和延展性(~ 10%)均比纯Zn合金高2倍。锌锶合金具有较好的体内外生物相容性和良好的抗菌性能。
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引用次数: 8
Recent progress on coatings of biomedical magnesium alloy 医用镁合金涂层研究进展
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2021.12.007
Peiduo Tong, Yulong Sheng, Ruiqing Hou, Mujahid Iqbal, Lan Chen, Jingan Li

Magnesium (Mg) alloy has received thorough attention in the biomedical field due to its excellent mechanical properties, good biocompatibility, and biodegradability. However, Mg alloy usually shows excessive degradation rate in the physiological environment owning to its active chemical nature. At the same time, the hydrogen generated by the degradation of Mg will increase the pH of local tissues, which will harm the growth of surrounding tissues. Given the above problems, it has become a research hotspot to obtain various properties of Mg alloy for clinical application by surface modification. In this paper, the surface coatings of Mg alloy are reviewed according to different types, including metals (metal oxides, metal hydroxides), inorganic non-metals, polymers (synthetic polymers and natural polymers), and composite coatings. The preparation methods, corrosion resistance, and biocompatibility of different types of coatings are discussed, and the development prospect of biomedical Mg alloy surface coatings is also predicted.

镁合金以其优异的力学性能、良好的生物相容性和可生物降解性在生物医学领域受到广泛关注。然而,镁合金由于其化学性质活泼,在生理环境中往往表现出过高的降解速率。同时,Mg降解产生的氢会使局部组织的pH升高,对周围组织的生长造成伤害。鉴于上述问题,通过表面改性获得镁合金的各种性能以供临床应用已成为研究热点。本文综述了镁合金表面涂层的研究进展,包括金属涂层(金属氧化物、金属氢氧化物)、无机非金属涂层、聚合物涂层(合成聚合物和天然聚合物)、复合涂层等。讨论了不同类型涂层的制备方法、耐腐蚀性和生物相容性,并对生物医用镁合金表面涂层的发展前景进行了展望。
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引用次数: 55
Signaling pathways implicated in enhanced stem/progenitor cell differentiation on electroactive scaffolds 电活性支架上干细胞/祖细胞分化增强的信号通路
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2021.11.003
Boon Chin Heng , Yunyang Bai , Xiaochan Li , Yanze Meng , Xuehui Zhang , Xuliang Deng

Cells are naturally surrounded by an electroactive extracellular matrix in vivo, which is composed of a diverse array of charged molecules such as glycosaminoglycans and proteoglycans, together with piezoelectric collagen fibers capable of generating electrical signals in response to mechanical stimuli. In recent years, electroactive scaffold materials have attracted much attention in tissue engineering and regenerative medicine applications, as a biomimetic strategy to recapitulate the natural physiological electrical microenvironment in vivo, which could enhance the differentiation of stem/progenitor cells into specific lineages, thus facilitating tissue repair and regeneration. The key to improving the functional design of electroactive scaffold biomaterials would be to understand the various intracellular signaling pathways that are activated by electrical stimuli. Therefore, this review critically examines the effects of electrical stimuli and/or scaffolds with electroactive properties on directing stem/progenitor cells towards the osteogenic, neurogenic and other lineages, with particular focus on the molecular signaling pathways involved.

细胞在体内自然被电活性细胞外基质包围,该基质由多种带电分子组成,如糖胺聚糖和蛋白聚糖,以及能够响应机械刺激产生电信号的压电胶原纤维。近年来,电活性支架材料作为一种再现体内自然生理电微环境的仿生策略,能够促进干细胞/祖细胞向特定谱系分化,从而促进组织修复和再生,在组织工程和再生医学应用中备受关注。改善电活性支架生物材料功能设计的关键是了解由电刺激激活的各种细胞内信号通路。因此,本文将重点研究电刺激和/或具有电活性的支架对引导干细胞/祖细胞向成骨、神经和其他谱系的影响,并特别关注所涉及的分子信号通路。
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引用次数: 8
Membrane fusion boosting drug transmembrane delivery 膜融合促进药物跨膜传递
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2022.01.009
Xing Gao, En Ren, Gang Liu

Benefiting from fusion element (peptides or proteins) anchoring, several biological membrane vesicles or synthetic liposomes have great potency to fuse with the target cell membrane via virus-mimetic behavior. When this process happens, the encapsulated cargos can be released directly into the cytoplasm together with membrane component (protein receptor, channel proteins, chemical receptors, antibodies) transfer, a process that facilitates cellular/molecular diagnosis and therapy.

得益于融合元素(多肽或蛋白质)的锚定,几种生物膜囊泡或合成脂质体通过模拟病毒的行为与靶细胞膜融合。当这一过程发生时,被封装的货物可以与膜成分(蛋白质受体、通道蛋白、化学受体、抗体)转移一起直接释放到细胞质中,这一过程有助于细胞/分子诊断和治疗。
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引用次数: 3
The increased ratio of Mg2+/Ca2+ from degrading magnesium alloys directs macrophage fate for functionalized growth of endothelial cells 来自降解镁合金的Mg2+/Ca2+比率的增加指导巨噬细胞的命运以实现内皮细胞的功能化生长
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2022.01.001
Ya-chen Hou , Frank Witte , Jingan Li , Shaokang Guan

Biomedical magnesium (Mg) alloys have been widely studied as important structural materials and biodegradable materials in cardiovascular stents system. However, excessively rapid degradation and delayed endothelialization are still the bottlenecks limiting the further application of Mg alloy stents. The core scientific problem lies in how Mg alloys and their degradation products direct the fate of cardiovascular cells to develop in favor of endothelialization, which is still unclear. The aggregation of macrophages (MA) is the earliest cellular response after stent implantation for atherosclerotic lesions, and our previous research proved that MA behaviors played crucial roles on endothelialization in vitro. Thus, the present study chooses a Mg alloy, Mg–Zn–Y-Nd, to investigate its degradation behavior on directing the fates of MA and endothelial cells (EC). Our data shows that the increased ratio of Mg2+/Ca2+ in medium during the degradation of the Mg–Zn–Y-Nd alloy may regulate the MA to switch to their M2 phenotype, and the MA conditioned medium further promote the proliferation and CD31 expression of EC in vitro. Co-culture of MA and EC indicates that M2-type MA also contribute to proliferation and CD31 expression of EC. All these results suggest controlling the degradation behavior of Mg alloys will direct the fates of MA and EC, further improving endothelialization in vitro.

医用镁合金作为重要的结构材料和生物降解材料在心血管支架系统中得到了广泛的研究。然而,过快的降解和延迟的内皮化仍然是限制镁合金支架进一步应用的瓶颈。核心的科学问题在于镁合金及其降解产物如何指导心血管细胞的命运,使其朝着有利于内皮化的方向发展,这一点尚不清楚。巨噬细胞(macrophages, MA)聚集是动脉粥样硬化病变支架植入后最早的细胞反应,我们前期的研究证实了巨噬细胞的行为在体外内皮化过程中起着至关重要的作用。因此,本研究选择Mg - zn - y - nd镁合金,研究其降解行为对MA和内皮细胞(EC)命运的影响。我们的数据表明,在Mg-Zn-Y-Nd合金降解过程中,培养基中Mg2+/Ca2+比例的增加可能调节MA向其M2表型转换,MA条件培养基进一步促进EC的体外增殖和CD31的表达。MA与EC共培养表明,m2型MA对EC的增殖和CD31表达也有促进作用。这些结果表明,控制镁合金的降解行为将指导MA和EC的命运,进一步改善体外内皮化。
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引用次数: 22
Twisted fiber batteries for wearable electronic devices 可穿戴电子设备用扭曲纤维电池
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2021.11.001
Yunru Yu , Xiaocheng Wang , Chaoyu Yang , Luoran Shang

Wearable electronic devices are important in recording signals related to human activities. Because the performance of wearable electronic devices depends heavily on power sources, batteries, especially fiber batteries have been attracting numerous attention in the past decades. Here, we present a perspective of fiber lithium-ion battery (FLIB) equipped with excellent energy supply, deformability, and feasibility to be woven into textile electronics. The scalable production and sustainable application of these FLIBs in health monitoring could be realized benefitting from the decreased internal resistance with length. This kind of fiber battery is anticipated to show its potentials in not only next-generation flexible devices but also regenerative medicine and tissue engineering.

可穿戴电子设备在记录与人类活动有关的信号方面非常重要。由于可穿戴电子设备的性能在很大程度上依赖于电源,在过去的几十年里,电池,特别是光纤电池已经引起了人们的广泛关注。在此,我们提出了一种光纤锂离子电池(FLIB)的前景,该电池具有良好的能量供应,可变形性和编织到纺织电子产品中的可行性。这些flib的内阻随长度的减小而减小,可实现规模化生产和可持续应用于健康监测。预计这种纤维电池不仅在下一代柔性器件上,而且在再生医学和组织工程上也有很大的潜力。
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引用次数: 4
B12-dependent photoreceptor protein as an emerging tool for materials synthetic biology B12依赖性光感受器蛋白作为材料合成生物学的新兴工具
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2022.03.004
Hong Kiu Francis Fok , Fei Sun

Controlling biomolecular interactions with light has gained traction among biomedical researchers due to its high spatiotemporal precision. Although a variety of photoresponsive chemical moieties are readily available thanks to the efforts made by chemists, genetically encoded photoswitches, also known as optogenetic tools, that are compatible with complex biological systems remain highly desirable. Recently, detailed mechanistic studies of the B12-dependent bacterial photoreceptor CarH have provided researchers with some new approaches to materials synthetic biology. Further development of this emerging molecular tool will continue to benefit future materials science and optogenetics.

控制生物分子与光的相互作用因其高时空精度而受到生物医学研究人员的关注。尽管由于化学家的努力,各种光敏化学成分很容易获得,但与复杂生物系统兼容的遗传编码光开关(也称为光遗传工具)仍然是非常需要的。近年来,b12依赖性细菌光感受器CarH的详细机理研究为材料合成生物学的研究提供了一些新的途径。这种新兴分子工具的进一步发展将继续有利于未来的材料科学和光遗传学。
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引用次数: 1
Stimuli-responsive materials: A smart way to study dynamic cell responses 刺激反应材料:一种研究动态细胞反应的聪明方法
Q1 Engineering Pub Date : 2022-01-01 DOI: 10.1016/j.smaim.2022.01.010
Maaike Bril , Sebastian Fredrich , Nicholas A. Kurniawan

Cells in the body reside within the extracellular matrix (ECM), a three-dimensional environment that not only provides structural support for the cells, but also influences cellular processes, like migration and differentiation. The ECM and the cells continuously engage in a complex and highly dynamic interplay, shaping both the matrix as well as the cellular outcome. To study these dynamic, bidirectional interactions in a systematic manner, the ability to dynamically control cellular environments is highly desirable. Stimuli-responsive materials are a class of materials that have been engineered to respond to external cues, e.g., light, electricity, or magnetic field, and therefore hold fascinating potentials as an ideal experimental platform to introduce changing spatiotemporal signals to cells. Here, we review the state of the art in stimuli-responsive materials and their design strategies, with an emphasis on the dynamic introduction of physical and mechanical cues. The effects of such dynamic stimuli on the responses of living cells are examined on three different levels: cellular phenotypes, intracellular and cytoskeletal changes, and nuclear and epigenetic effects. Finally, we discuss the current challenges and limitations as well as the potential outlooks in exploiting stimuli-responsive biomaterials.

细胞位于细胞外基质(ECM)中,这是一个三维环境,不仅为细胞提供结构支持,而且影响细胞过程,如迁移和分化。ECM和细胞不断地进行复杂和高度动态的相互作用,形成基质和细胞结果。为了以系统的方式研究这些动态的、双向的相互作用,动态控制细胞环境的能力是非常可取的。刺激响应材料是一类被设计成对光、电或磁场等外部信号做出反应的材料,因此作为向细胞引入变化的时空信号的理想实验平台,具有迷人的潜力。在这里,我们回顾了刺激反应材料及其设计策略的最新进展,重点介绍了物理和机械线索的动态引入。这些动态刺激对活细胞反应的影响在三个不同的水平上进行了研究:细胞表型,细胞内和细胞骨架变化,以及核和表观遗传效应。最后,我们讨论了当前的挑战和限制以及开发刺激反应生物材料的潜在前景。
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引用次数: 19
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Smart Materials in Medicine
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