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Mechanically strong porous bioceramic tubes facilitate large segmental bone defect repair by providing long-term structurally stability and promoting osteogenesis 机械强度强的多孔生物陶瓷管通过提供长期结构稳定性和促进成骨促进大节段骨缺损修复
Q1 Medicine Pub Date : 2023-10-24 DOI: 10.1016/j.engreg.2023.10.001
Lijun Xie , Jiahao Zhang , Hangxiang Sun , Zehao Chen , Wangsiyuan Teng , Xupeng Chai , Cong Wang , Xianyan Yang , Yifan Li , Sanzhong Xu , Zhongru Gou , Zhaoming Ye

Mechanically strong magnesium-doped Ca-silicate bioceramic scaffolds have many advantages in repairing large segmental bone defects. Herein we combine β-TCP with 6 mol% magnesium-doped calcium silicate (Mg6) at three different ratios (TCP, TCP+15 %Mg6, TCP+85 %Mg6) to find an appropriate ratio which can exert considerable influence on bone regeneration. In this study, the bioceramic scaffolds were assessed for mechanical strength, bioactive ion release, biocompatibility, and osteogenic capacity through in vitro testing. Additionally, the potential for promoting bone regeneration was investigated through in vivo implantation of porous tube-like scaffolds. The results showed that the compressive strength increased with the augmentation of Mg6 component. Especially the compressive strength of the TCP+85 %Mg6 group reached 38.1 ± 3.8 MPa, three times that of the other two groups. Furthermore, extensive in vivo investigations revealed that the TCP+85 %Mg6 bioceramic scaffolds were particularly beneficial for the osteogenic capacity of critical-sized femoral defects (20 mm in length). Altogether, magnesium doping in bioceramic implants is a promising strategy to provide stronger mechanical support and enhance osteogenesis to accelerate the repair of large defects.

机械强度强的镁掺杂硅酸钙生物陶瓷支架在修复大块骨缺损方面具有许多优点。在此,我们将β-TCP与6mol%镁掺杂的硅酸钙(Mg6)以三种不同的比例(TCP、TCP+15%Mg6、TCP+85%Mg6)相结合,以找到一个合适的比例,该比例可以对骨再生产生相当大的影响。在本研究中,通过体外测试评估了生物陶瓷支架的机械强度、生物活性离子释放、生物相容性和成骨能力。此外,通过体内植入多孔管状支架研究了促进骨再生的潜力。结果表明,随着Mg6组分的增加,抗压强度增加。特别是TCP+85%Mg6组的抗压强度达到38.1±3.8MPa,是其他两组的三倍。此外,广泛的体内研究表明,TCP+85%Mg6生物陶瓷支架对临界尺寸股骨缺损(长度20mm)的成骨能力特别有益。总之,在生物陶瓷植入物中掺镁是一种很有前途的策略,可以提供更强的机械支撑,增强成骨能力,加速大缺陷的修复。
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引用次数: 0
Engineered artificial skins: Current construction strategies and applications 工程人造皮肤:当前的施工策略和应用
Q1 Medicine Pub Date : 2023-09-30 DOI: 10.1016/j.engreg.2023.09.001
Ye Xu , Xiangyi Wu , Yuanyuan Zhang , Yunru Yu , Jingjing Gan , Qian Tan

Skin damage resulting from burns, injuries, or diseases can lead to significant functional and esthetic deficits. However, traditional treatments, such as skin grafting, have limitations including limited donor skin availability, poor aesthetics, and functional impairment. Skin tissue engineering provides a promising alternative, with engineered artificial skins offering a highly viable avenue. Engineered artificial skin is designed to mimic or replace the functions of natural human skin and find applications in various medical treatments, particularly for severe burns, chronic wounds, and other skin injuries or defects. These artificial skins aim to promote wound healing, provide temporary coverage, permanent skin replacement, and restore the skin's barrier function. Artificial skins have diverse applications in medicine and wound care, addressing burns, chronic wounds, and traumatic injuries. They also serve as valuable tools for research in tissue engineering, offering experimental models for studying wound healing mechanisms, testing new biomaterials, and exploring innovative approaches to skin regeneration. This review provides an overview of current construction strategies for engineered artificial skin, including cell sources, biomaterials, and construction techniques. It further explores the primary application areas and future prospects of artificial skin, highlighting their potential to revolutionize skin reconstruction and advance the field of regenerative medicine.

烧伤、损伤或疾病引起的皮肤损伤可导致严重的功能和审美缺陷。然而,传统的治疗方法,如皮肤移植,有局限性,包括供体皮肤可用性有限、美观性差和功能受损。皮肤组织工程提供了一种很有前途的替代品,工程人造皮肤提供了一条高度可行的途径。工程人造皮肤旨在模仿或取代天然人类皮肤的功能,并应用于各种医疗治疗,特别是严重烧伤、慢性伤口和其他皮肤损伤或缺陷。这些人造皮肤旨在促进伤口愈合,提供临时覆盖、永久性皮肤替代,并恢复皮肤的屏障功能。人造皮肤在医学和伤口护理中有着不同的应用,包括烧伤、慢性伤口和创伤。它们也是组织工程研究的宝贵工具,为研究伤口愈合机制、测试新的生物材料和探索皮肤再生的创新方法提供了实验模型。这篇综述概述了目前工程人工皮肤的构建策略,包括细胞来源、生物材料和构建技术。它进一步探索了人造皮肤的主要应用领域和未来前景,突出了它们在彻底改变皮肤重建和推进再生医学领域的潜力。
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引用次数: 1
Strategies for engineering neural cell alignment and their biomedical applications 神经细胞排列的工程策略及其生物医学应用
Q1 Medicine Pub Date : 2023-09-29 DOI: 10.1016/j.engreg.2023.09.002
Nan Xia , Rui Liu , Weiwei Chen , Dandan Wang , Lingyun Sun

Cell alignment plays a vital role in tissue regeneration, especially for neural cells like neurons. Recent progress in biomaterial technologies has enabled the creation of various approaches for engineering neural cell alignment, which has demonstrated significant effectiveness in several biomedical applications. This review primarily concentrates on the latest advancements for in vitro engineering of neural cell alignment. We also summarized their applications in biomedical research, particularly their potential in addressing nervous system injuries. Finally, we analyze the current challenges associated with engineering neural cell alignment and provide insights into future perspectives in this field.

细胞排列在组织再生中起着至关重要的作用,尤其是对神经元等神经细胞来说。生物材料技术的最新进展使神经细胞排列工程的各种方法得以创造,这在一些生物医学应用中表现出了显著的有效性。这篇综述主要集中于神经细胞排列体外工程的最新进展。我们还总结了它们在生物医学研究中的应用,特别是它们在解决神经系统损伤方面的潜力。最后,我们分析了当前与工程神经细胞排列相关的挑战,并对该领域的未来前景提供了见解。
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引用次数: 0
Biomimetic extracellular vesicles for the tumor targeted treatment 用于肿瘤靶向治疗的仿生细胞外囊泡
Q1 Medicine Pub Date : 2023-09-05 DOI: 10.1016/j.engreg.2023.08.002
Ruolin Shi , An Zhan , Xinze Li , Bin Kong , Gaofeng Liang

Extracellular vesicles (EVs) are nanoscale substances produced by most cells, which were not fully understood in the early years. However, with the development of advanced techniques, researchers have discovered that EVs play an essential role in information exchange and signal transduction between cells. Nowadays, EVs are being used, modified, and developed as a natural drug carrier in various medical fields because of their high biocompatibility and natural affinity with the source body. Many studies have shown that multiple sources of EVs have been modified and utilized in cancer therapy to improve patients' treatment windows and effectively prolong patient survival. In this paper, we review the advances in the treatment of cancer based on EVs. We summarize the types of EVs loading therapy, the modes of drug loading and the latest therapeutic applications of multiple modes combined with EVs in cancer treatment. We conclude with a discussion of the current status, challenges, and prospects of EVs as a tool for tumor therapy.

细胞外囊泡(EVs)是由大多数细胞产生的纳米级物质,早期尚未完全了解。然而,随着先进技术的发展,研究人员发现电动汽车在细胞间的信息交换和信号转导中起着至关重要的作用。目前,电动汽车因其高生物相容性和与源体的天然亲和力,作为一种天然的药物载体,在各个医学领域得到了应用、改造和发展。许多研究表明,多种来源的电动汽车已被改造并用于癌症治疗,以改善患者的治疗窗口期,有效延长患者的生存期。本文就ev治疗癌症的研究进展作一综述。本文综述了ev载药治疗的类型、载药方式以及多种载药方式联合ev在癌症治疗中的最新应用。最后,我们讨论了ev作为肿瘤治疗工具的现状、挑战和前景。
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引用次数: 0
Understanding the interplay between cell force and cell adhesion processes 了解细胞力和细胞粘附过程之间的相互作用
Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.engreg.2023.04.002
Peng Wang , Jie Li , Qiang Wei

Cells, wrapped among their neighbors and surrounding extracellular matrix (ECM), form cell-cell adhesions and cell-ECM adhesions. Extracellular biophysical cues exert a far-reaching influence on a sweeping of cell behaviors, including signal transduction, gene expression, and fate determination. Cell-cell adhesions mediated by intercellular adhesion molecules bridge the membranes of adjacent cells through either heterophilic or homophilic adhesive interactions, playing a critical part in multicellular structural maintenance and, therefore, a foundation for multicellular organisms. Cell-ECM adhesions are derived from the interaction between cell adhesion receptors and multi-adhesive matrix proteins to ensure cell and tissue cohesion. Whereas cells not only unilaterally respond to certain cues from extracellular environment but can also alter the physicochemical profiles of the externalities and hence hold important implications for clinical applications. The essential function of cell adhesions has created tremendous interests in developing methods for measuring and studying cell adhesion properties, namely, cellular force. Here, we describe the collection of cell adhesive inputs on cellular signaling cascades and the “crosstalk” between cell-cell adhesions and cell-ECM adhesions. Furthermore, we provide the summary of the current methods to measure such cell adhesive forces.

细胞被周围细胞外基质(ECM)包裹,形成细胞-细胞黏附和细胞-ECM黏附。细胞外生物物理信号对一系列细胞行为产生深远的影响,包括信号转导、基因表达和命运决定。细胞间黏附分子介导的细胞-细胞黏附通过嗜异性或嗜同性的黏附相互作用在相邻细胞的细胞膜上架起桥梁,在多细胞结构维持中起着关键作用,因此是多细胞生物的基础。细胞- ecm黏附源于细胞黏附受体和多黏附基质蛋白之间的相互作用,以确保细胞和组织的黏附。然而,细胞不仅对来自细胞外环境的某些线索作出单方面的反应,而且还可以改变外部性的物理化学特征,因此对临床应用具有重要意义。细胞粘附的基本功能引起了人们对开发测量和研究细胞粘附特性(即细胞力)的方法的极大兴趣。在这里,我们描述了细胞信号级联中细胞粘附输入的收集以及细胞-细胞粘附和细胞- ecm粘附之间的“串扰”。此外,我们还总结了目前测量这种细胞粘附力的方法。
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引用次数: 1
Rassf2 overexpression mediated by AAV promotes the supporting cell-to-hair cell transformation in the cochlea AAV介导的Rassf2过表达促进耳蜗支持细胞向毛细胞转化
Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.engreg.2023.04.003
Liyan Zhang , Jieyu Qi , Yuan Fang , Fangzhi Tan , Yinyi Zhou , Ziyu Zhang , Qiuhan Sun , Nianci Li , Yideng Huang , Jingwu Sun , Renjie Chai

Sensory hair cells are responsible for detecting and transmitting sound in the inner ear, and damage to HCs leads to hearing loss. HCs do not regenerate spontaneously in adult mammals, which makes the hearing loss permanent. However, hair cells and supporting cells have the same precursors in the inner ear, and in newborn mice, the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells. Here, we demonstrate the role of the Ras association domain family member 2 (Rassf2) in supporting cell to hair cell trans-differentiation in the inner ear. Using the AAV vector (AAV-ie) to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids. Also, AAV-Rassf2 enhanced the regenerative ability of Lgr5+ SCs in the postnatal cochlea without impairing hearing, and this might due to the modulation of the Wnt, Hedgehog and Notch signaling pathways. Furthermore, AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model. In summary, our results suggest that Rassf2 is a key component in HC regenerative repair, and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.

感觉毛细胞负责探测和传递内耳的声音,对毛细胞的损害会导致听力丧失。成年哺乳动物的hc不能自发再生,这使得听力损失成为永久性的。然而,毛细胞和支持细胞在内耳中具有相同的前体,并且在新生小鼠中,相邻的SCs可以通过基因操作激活,分化为新再生的毛细胞。在这里,我们证明了Ras关联结构域家族成员2 (Rassf2)在支持内耳细胞向毛细胞的转分化中的作用。利用AAV载体(AAV-ie)上调Rassf2表达可促进人工耳蜗类器官的支持细胞分裂和毛细胞生成。此外,AAV-Rassf2在不损害听力的情况下增强了出生后耳蜗Lgr5+ SCs的再生能力,这可能与Wnt、Hedgehog和Notch信号通路的调节有关。此外,AAV-Rassf2在新霉素损伤模型中促进耳蜗支持细胞分裂和毛细胞生成。综上所述,我们的研究结果表明Rassf2是HC再生修复的关键成分,由腺相关病毒介导的基因调节可能是一种很有前景的听力修复基因治疗方法。
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引用次数: 0
One-step and wash-free multiplexed immunoassay platform based on bioinspired photonic barcodes 基于仿生光子条形码的一步免清洗多重免疫分析平台
Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.engreg.2023.03.007
Dagan Zhang , Yuze Wang , Junqi Zhao , Xueqin Li , Yuanyang Zhou , Sen Wang

Multiplex, rapid and accurate virus quantification plays a great value in biomedical detection. Here, a novel one step, wash-free immunoassay platform based bioinspired PhC barcodes for multiplexed virus quantification was explored. PhC barcodes were decorated with PDA by self-polymerization of DA, thus this nanocomposite hybridized PhC barcodes facilitated the adsorption of FITC labelled antibodies and quenched itself photoluminescent, allowing a fast responsive composite platform. In the presence of target analyte, the FITC-labelled detection antibody was released from the surface of PDA decorated microcarrier to specifically bind to the target analyte, thus recovered the photoluminescence. In addition, the PhC microcarrier was enabled to carry out various color barcode for different targets detection though tuning internal periodic structures. Based on these excellent performances of the nanocomposite barcode, this method can not only capture H1N1, H5N1, SARS-CoV-2 simultaneously with rapid, accuracy but also accomplish multiplex quantification detection with high-sensitivity. Furthermore, our developed platform was also achieved with high-sensitivity and high-specificity through the verification of clinical samples, thus laying out a new avenue for multiplex virus detection in clinical diagnosis.

多重、快速、准确的病毒定量在生物医学检测中具有重要价值。在这里,我们探索了一种新的一步,免洗免疫分析平台,基于生物启发的PhC条形码,用于多路病毒定量。通过DA自聚合修饰PDA修饰PhC条形码,使得该纳米复合杂化PhC条形码能够吸附FITC标记的抗体并淬灭自身光致发光,从而实现了快速响应的复合平台。在目标分析物存在的情况下,fitc标记的检测抗体从PDA修饰的微载体表面释放,特异性结合目标分析物,从而恢复光致发光。此外,通过调整内部周期结构,使PhC微载体能够进行不同颜色的条形码,用于不同的目标检测。基于纳米复合条形码的这些优良性能,该方法不仅可以快速、准确地同时捕获H1N1、H5N1、SARS-CoV-2,而且可以实现高灵敏度的多重定量检测。此外,通过临床样本的验证,我们开发的平台也实现了高灵敏度和高特异性,从而为临床诊断中的多重病毒检测开辟了新的途径。
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引用次数: 1
Developing hierarchical microneedles for biomedical applications 开发用于生物医学应用的分级微针
Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.engreg.2023.04.004
Minhui Lu , Xiaoxuan Zhang , Zhiqiang Luo , Yuanjin Zhao

As a new kind of microcarrier device, microneedles are featured by micrometer needle arrays with an overall size in the centimeter scale. Due to the needle shape and the micron size, microneedles can penetrate the skin without harming nerves and blood vessels, which causes many advantages such as minimally invasive, safe and convenient. The past few decades have witnessed a great leap in microneedles research. The main materials of microneedles have changed from metal and ceramic to polymers with more complex functions, and the optimization of materials and preparation strategies has led to a greater variety of microneedle styles. Among them, the construction or combination of smaller size structures or materials on microneedles to fabricate hierarchical microneedles is a major research hotspot. Here, we present the recent research progress of hierarchical microneedles for biomedicine. We begin by discussing the fabrication strategies of hierarchical microneedles, including mainstream casting and coating methods based on microneedle molds and three dimensions (3D) printing methods. We then expand the discussion from the hierarchical microneedles with porous structure to those composited with nanomaterials. Eventually, we have a discussion about the research progress of hierarchical microneedles in the area of biomarkers detection and transdermal drug delivery, as well as its future development direction.

微针是一种新型的微载体器件,其特点是微米级的针阵列,整体尺寸在厘米级。由于针头的形状和微米大小,微针可以穿透皮肤而不伤害神经和血管,从而具有微创,安全,方便等诸多优点。过去几十年见证了微针研究的巨大飞跃。微针的主要材料已经从金属和陶瓷转变为功能更复杂的聚合物,材料和制备策略的优化使得微针的样式更加多样。其中,在微针上构建或组合更小尺寸的结构或材料来制造分层微针是一个主要的研究热点。本文就分层微针在生物医学领域的研究进展作一综述。我们首先讨论了分层微针的制造策略,包括基于微针模具的主流铸造和涂层方法以及三维(3D)打印方法。然后,我们将讨论从具有多孔结构的分层微针扩展到与纳米材料复合的微针。最后,我们讨论了分层微针在生物标志物检测和透皮给药领域的研究进展,以及未来的发展方向。
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引用次数: 0
Autophagy mediates osteoporotic bone regeneration induced by micro-/nano-structured modification on hydroxyapatite bioceramics 自噬介导羟基磷灰石生物陶瓷微/纳米结构修饰诱导的骨质疏松性骨再生
Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.engreg.2023.03.003
Jinjie Cui , Xinran Zhang , Liming Cheng , Kaili Lin

Osteoporosis (OP) is an age-related disease of bone metabolism, characterized by bone mass loss and bone microarchitecture deterioration, the poor osteogenesis microenvironment of OP caused hardly repairing of the bone defects. As a dynamic process to fuel cellular renovation, autophagy has been proved to play a vital role in regulating cell differentiation and maintaining bone homeostasis. Traditional bone repairing biomaterials are hardly repairing the bone defects under OP pathological microenvironment. Therefore, it is essential to development novel biomaterials to improve osteoporotic osteogenesis. Compared to biochemical cues, biophysical cues exhibited more advantages in biocompatible and side effects. Herein, inspired by the importance of enhanced autophagic response in osteoporotic environment, we intend to utilize the micro-/nano-structured hydroxyapatite (mnHA) bioceramics as the mimic structure of natural bone tissue to regulate autophagic activity in ovariectomy bone mesenchymal stem cells (OVX-BMSCs), finally promote to bone regeneration in OP condition. The results indicated that mnHA bioceramics promoted cell adhesion and osteogenesis of OVX-BMSCs, and enhanced autophagy level in OVX-BMSCs. In the calvarial defects of OVX-rats, the mnHA scaffold acquired excellent bone repair effect. According to the current findings, regulating the level of autophagy could be a promising strategy for improve osteoporotic osteogenesis in the future.

骨质疏松症(Osteoporosis, OP)是一种与年龄相关的骨代谢疾病,以骨量丢失和骨微结构恶化为特征,OP成骨微环境差导致骨缺损难以修复。自噬作为一种促进细胞更新的动态过程,在调节细胞分化和维持骨稳态中起着至关重要的作用。传统的骨修复生物材料难以修复OP病理微环境下的骨缺损。因此,开发新型生物材料促进骨质疏松成骨是十分必要的。与生化线索相比,生物物理线索在生物相容性和副作用方面表现出更大的优势。鉴于骨质疏松环境中增强自噬反应的重要性,我们打算利用微/纳米结构的羟基磷灰石(mnHA)生物陶瓷作为天然骨组织的模拟结构,调节卵巢切除骨间充质干细胞(OVX-BMSCs)的自噬活性,最终促进OP条件下的骨再生。结果表明,mnHA生物陶瓷能促进OVX-BMSCs的细胞粘附和成骨,增强OVX-BMSCs的自噬水平。在ovx大鼠颅骨缺损中,mnHA支架获得了良好的骨修复效果。根据目前的研究结果,调节自噬水平可能是未来改善骨质疏松性成骨的一种有希望的策略。
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引用次数: 1
Accelerated neutral atom beam (ANAB) and gas clustered ion beam (GCIB) treatment of implantable device polymers leads to decreased bacterial attachment in vitro and decreased inflammation in vivo 可植入装置聚合物的加速中性原子束(ANAB)和气体簇离子束(GCIB)治疗可减少体外细菌附着和体内炎症
Q1 Medicine Pub Date : 2023-09-01 DOI: 10.1016/j.engreg.2023.03.006
Joseph Khoury , Ti Zhang , David B. Earle , M. Laird Forrest

Infections at the placement site of biomaterial-based devices and subsequent scar formation results in morbidity, which may require revision surgery. Biomaterials intended for permanent implantation in the body need to be biologically inert to avoid excessive foreign body response and to reduce bacterial attachment. In this study, we show that polymeric materials commonly used in medical devices, including polyetheretherketone (PEEK) and polypropylene, treated by gas cluster ion beam (GCIB) or by accelerated neutral atom beam (ANAB) result in a nanoscale-modified surface topography that changes the ability of extracellular proteins to bind. This leads to decreased bacterial attachment and an attenuated inflammatory response using both in vitro and in vivo assays. Differential adsorption of extracellular proteins to the polymeric surface improved the competitive attachment of osteoblasts over bacteria, without resorting to growth factor of antibiotic use.

基于生物材料的装置放置部位的感染和随后的疤痕形成会导致发病率,这可能需要翻修手术。用于永久植入体内的生物材料需要具有生物惰性,以避免过多的异物反应并减少细菌附着。在这项研究中,我们展示了医疗器械中常用的聚合物材料,包括聚醚醚酮(PEEK)和聚丙烯,通过气团离子束(GCIB)或加速中性原子束(ANAB)处理,可以产生纳米级修饰的表面形貌,从而改变细胞外蛋白质结合的能力。这导致减少细菌附着和减轻炎症反应使用体外和体内试验。细胞外蛋白对聚合物表面的差异吸附改善了成骨细胞对细菌的竞争性附着,而无需诉诸抗生素使用的生长因子。
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引用次数: 0
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Engineered regeneration
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