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Microarray analysis of signalling interactions between inflammation and angiogenesis in subchondral bone in temporomandibular joint osteoarthritis. 颞下颌关节骨关节炎软骨下骨中炎症与血管生成之间信号相互作用的芯片分析。
Pub Date : 2024-06-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.02.007
Wenpin Qin, Jialu Gao, Jianfei Yan, Xiaoxiao Han, Weicheng Lu, Zhangyu Ma, Lina Niu, Kai Jiao

Inflammation and angiogenesis, the major pathological changes of osteoarthritis (OA), are closely associated with joint pain; however, pertinent signalling interactions within subchondral bone of osteoarthritic joints and potential contribution to the peripheral origin of OA pain remain to be elucidated. Herein we developed a unilateral anterior crossbite mouse model with osteoarthritic changes in the temporomandibular joint. Microarray-based transcriptome analysis, besides quantitative real-time polymerase chain reaction, was performed to identify differentially expressed genes (DEGs). Overall, 182 DEGs (fold change ≥ 2, P < 0.05) were identified between the control and unilateral anterior crossbite groups: 168 were upregulated and 14 were downregulated. On subjecting significant DEGs to enrichment analyses, inflammation and angiogenesis were identified as the most affected. Inflammation-related DEGs were mainly enriched in T cell activation and differentiation and in the mammalian target of rapamycin/nuclear factor-κB/tumour necrosis factor signalling. Furthermore, angiogenesis-related DEGs were mainly enriched in the Gene Ontology terms angiogenesis regulation and vasculature development and in the KEGG pathways of phosphoinositide 3-kinase-protein kinase B/vascular endothelial growth factor/hypoxia-inducible factor 1 signalling. Protein-protein interaction analysis revealed a close interaction between inflammation- and angiogenesis-related DEGs, suggesting that phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Pi3kcd), cathelicidin antimicrobial peptide (Camp), C-X-C motif chemokine receptor 4 (Cxcr4), and MYB proto-oncogene transcription factor (Myb) play a central role in their interaction. To summarize, our findings reveal that in subchondral bone of osteoarthritic joints, signal interaction is interrelated between inflammation and angiogenesis and associated with the peripheral origin of OA pain; moreover, our data highlight potential targets for the inhibition of OA pain.

炎症和血管生成是骨关节炎(OA)的主要病理变化,与关节疼痛密切相关;然而,骨关节炎关节软骨下骨中的相关信号相互作用以及对 OA 疼痛外周起源的潜在贡献仍有待阐明。在此,我们建立了一个单侧前交叉咬合小鼠模型,该模型的颞下颌关节发生了骨关节炎变化。除了定量实时聚合酶链反应外,我们还进行了基于芯片的转录组分析,以确定差异表达基因(DEGs)。总体而言,在对照组和单侧前交叉咬合组之间发现了 182 个 DEGs(折叠变化≥ 2,P < 0.05):168 个上调,14 个下调。对重要的 DEGs 进行富集分析后发现,炎症和血管生成受影响最大。与炎症相关的 DEGs 主要富集在 T 细胞活化和分化以及雷帕霉素哺乳动物靶标/核因子-κB/肿瘤坏死因子信号传导中。此外,与血管生成相关的 DEGs 主要富集在基因本体(Gene Ontology)术语 "血管生成调控 "和 "血管发育 "以及 KEGG 通路 "磷酸肌醇 3- 激酶-蛋白激酶 B/血管内皮生长因子/缺氧诱导因子 1 信号传导 "中。蛋白-蛋白相互作用分析显示,炎症和血管生成相关的DEGs之间存在密切的相互作用,表明磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基δ(Pi3kcd)、cathelicidin抗菌肽(Camp)、C-X-C motif趋化因子受体4(Cxcr4)和MYB原癌基因转录因子(Myb)在它们之间的相互作用中起着核心作用。总之,我们的研究结果表明,在骨关节炎关节软骨下骨中,炎症和血管生成之间存在信号相互作用,并与 OA 疼痛的外周起源有关;此外,我们的数据还突出了抑制 OA 疼痛的潜在靶点。
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引用次数: 0
Engineering vascularised organoid-on-a-chip: strategies, advances and future perspectives. 片上血管有机体工程:战略、进展和未来展望。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.003
Zhangjie Li, Dingyuan Yu, Chenyang Zhou, Feifan Wang, Kangyi Lu, Yijun Liu, Jiaqi Xu, Lian Xuan, Xiaolin Wang

In recent years, advances in microfabrication technology and tissue engineering have propelled the development of a novel drug screening and disease modelling platform known as organoid-on-a-chip. This platform integrates organoids and organ-on-a-chip technologies, emerging as a promising approach for in vitro modelling of human organ physiology. Organoid-on-a-chip devices leverage microfluidic systems to simulate the physiological microenvironment of specific organs, offering a more dynamic and flexible setting that can mimic a more comprehensive human biological context. However, the lack of functional vasculature has remained a significant challenge in this technology. Vascularisation is crucial for the long-term culture and in vitro modelling of organoids, holding important implications for drug development and personalised medical approaches. This review provides an overview of research progress in developing vascularised organoid-on-a-chip models, addressing methods for in vitro vascularisation and advancements in vascularised organoids. The aim is to serve as a reference for future endeavors in constructing fully functional vascularised organoid-on-a-chip platforms.

近年来,微细加工技术和组织工程学的进步推动了一种新型药物筛选和疾病建模平台--"类器官芯片 "的发展。该平台整合了类器官和片上器官技术,是一种很有前景的体外模拟人体器官生理学的方法。类器官芯片设备利用微流体系统模拟特定器官的生理微环境,提供了一个更动态、更灵活的环境,可以模拟更全面的人体生物环境。然而,缺乏功能性血管一直是这项技术面临的重大挑战。血管化对器官组织的长期培养和体外建模至关重要,对药物开发和个性化医疗方法具有重要意义。这篇综述概述了开发血管化芯片有机体模型的研究进展,探讨了体外血管化的方法和血管化有机体的进展。目的是为未来构建全功能血管化类器官芯片平台提供参考。
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引用次数: 0
Harnessing exosomes for targeted therapy: strategy and application. 利用外泌体进行靶向治疗:策略与应用。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.005
Xiaoxiang Ren, Ruixue Xu, Chenjie Xu, Jiacan Su

Exosomes, nanoscopic extracellular vesicles produced by cells, are pivotal in mediating intracellular communication by transporting nucleic acids, proteins, lipids, and other bioactive molecules, thereby influencing physiological and pathological states. Their endogenous origin and inherent diversity confer distinct advantages over synthetic vehicles like liposomes and nanoparticles in diagnostic and therapeutic applications. Despite their potential, the clinical utility of exosomes is hampered by challenges such as limited storage stability, yield, purity, and targeting efficiency. This review focuses on exosomes as targeted therapeutic agents, examining their biogenesis, classification, isolation, and characterisation, while also addressing the current limitations in yield, purity, and targeting. We delve into the literature to propose optimisation strategies that can enhance their therapeutic efficacy and accelerate the translation of exosome-based therapies into clinical practice.

外泌体是细胞产生的纳米级细胞外囊泡,通过运输核酸、蛋白质、脂质和其他生物活性分子,在介导细胞内交流方面发挥着关键作用,从而影响生理和病理状态。在诊断和治疗应用中,与脂质体和纳米颗粒等合成载体相比,小体的内源性来源和固有多样性具有明显优势。尽管外泌体潜力巨大,但其临床应用却受到存储稳定性、产量、纯度和靶向效率等方面挑战的制约。本综述侧重于外泌体作为靶向治疗药物,研究其生物发生、分类、分离和表征,同时探讨目前在产量、纯度和靶向性方面的局限性。我们深入研究文献,提出优化策略,以提高外泌体的疗效,加快将基于外泌体的疗法转化为临床实践。
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引用次数: 0
Advances in magnesium-containing bioceramics for bone repair. 用于骨修复的含镁生物陶瓷的进展。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.002
Lei Qi, Tong Zhao, Jinge Yan, Weiwen Ge, Weidong Jiang, Jing Wang, Mazaher Gholipourmalekabadi, Kaili Lin, Xiuhui Wang, Lei Zhang

Reconstruction of bone defects or fractures caused by ageing, trauma and tumour resection is still a great challenge in clinical treatment. Although autologous bone graft is considered as gold standard, the source of natural bone is limited. In recent years, regenerative therapy based on bioactive materials has been proposed for bone reconstruction. Specially, numerous studies have indicated that bioactive ceramics including silicate and phosphate bioceramics exhibit excellent osteoinductivity and osteoconductivity, further promote bone regeneration. In addition, magnesium (Mg) element, as an indispensable mineral element, plays a vital role in promoting bone mineralisation and formation. In this review, different types of Mg-containing bioceramics including Mg-containing calcium phosphate-based bioceramics (such as Mg-hydroxyapatite, Mg-biphasic calcium phosphate), Mg-containing calcium silicate-based bioceramics (such as Mg2SiO4, Ca2MgSi2O7 and Mg-doped bioglass), Mg-based biocements, Mg-containing metal/polymer-bioceramic composites were systematacially summarised. Additionally, the fabrication technologies and their materiobiological effects were deeply discussed. Clinical applications and perspectives of magnesium-containing bioceramics for bone repair are highlighted. Overall, Mg-containing bioceramics are regarded as regenerative therapy with their optimised performance. Furthermore, more in-depth two-way researches on their performance and structure are essential to satisfy their clinical needs.

重建因衰老、创伤和肿瘤切除造成的骨缺损或骨折仍是临床治疗中的一大挑战。虽然自体骨移植被认为是金标准,但天然骨的来源有限。近年来,人们提出了基于生物活性材料的骨重建再生疗法。特别是,大量研究表明,包括硅酸盐和磷酸盐生物陶瓷在内的生物活性陶瓷具有良好的骨诱导性和骨传导性,可进一步促进骨再生。此外,镁(Mg)元素作为一种不可或缺的矿物质元素,在促进骨矿化和骨形成方面起着至关重要的作用。在这篇综述中,系统总结了不同类型的含镁生物陶瓷,包括含镁磷酸钙基生物陶瓷(如羟基磷灰石镁、双相磷酸钙镁)、含镁硅酸钙基生物陶瓷(如 Mg2SiO4、Ca2MgSi2O7 和掺镁生物玻璃)、镁基生物水泥、含镁金属/聚合物生物陶瓷复合材料。此外,还深入讨论了制造技术及其材料生物学效应。重点介绍了含镁生物陶瓷在骨修复方面的临床应用和前景。总之,含镁生物陶瓷以其优化的性能被视为一种再生疗法。此外,对其性能和结构进行更深入的双向研究对于满足临床需求至关重要。
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引用次数: 0
Enhanced angiogenesis in porous poly(ε-caprolactone) scaffolds fortified with methacrylated hyaluronic acid hydrogel after subcutaneous transplantation. 皮下移植后多孔聚(ε-己内酯)支架与甲基丙烯酸透明质酸水凝胶的血管生成得到增强
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.006
Huaxin Yang, Mengjia Zheng, Yuyue Zhang, Chaochang Li, Joseph Ho Chi Lai, Qizheng Zhang, Kannie Wy Chan, Hao Wang, Xin Zhao, Zijiang Yang, Chenjie Xu

A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment, survival, and retention in cell transplantation processes. This study presents a composite scaffold made of poly(ε-caprolactone) (PCL) and methacrylated hyaluronic acid (MeHA) hydrogel and describes the corresponding physical properties (surface area, porosity, and mechanical strength) and host response (angiogenesis and fibrosis) after subcutaneous transplantation. Specifically, we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities. Subsequently, we construct a series of PCL/MeHA composite scaffolds by combining these hydrogels and scaffolds. In experiments with mice, the scaffold composed of 3% PCL and 10-100 kDa, degree of substitution 70% MeHA results in the least fibrosis and a higher degree of angiogenesis. This study highlights the potential of PCL/MeHA composite scaffolds for subcutaneous cell transplantation, given their desirable physical properties and host response.

在细胞移植过程中,由多孔支架和水凝胶填充物组成的复合支架可促进细胞的移植、存活和保留。本研究提出了一种由聚ε-己内酯(PCL)和甲基丙烯酸透明质酸(MeHA)水凝胶组成的复合支架,并描述了其相应的物理性质(表面积、孔隙率和机械强度)和皮下移植后的宿主反应(血管生成和纤维化)。具体来说,我们合成了不同替代度的 MeHA,并制作了不同孔隙率的 PCL 支架。随后,我们结合这些水凝胶和支架,构建了一系列 PCL/MeHA 复合支架。在小鼠实验中,由 3% PCL 和 10-100 kDa、替代度为 70% 的 MeHA 组成的支架纤维化程度最低,血管生成程度较高。这项研究强调了 PCL/MeHA 复合支架在皮下细胞移植方面的潜力,因为它们具有理想的物理特性和宿主反应。
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引用次数: 0
Generation artificial intelligence (GenAI) and Biomaterials Translational: steering innovation without misdirection. 新一代人工智能(GenAI)和生物材料转化:引导创新而不误导。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.001
Long Bai, Zhidao Xia, James T Triffitt, Jiacan Su
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引用次数: 0
HIF-1α: linking subchondral bone and cartilage as a therapeutic target in osteoarthritis. HIF-1α:连接软骨下骨和软骨的骨关节炎治疗靶点。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.010
Kaibo Zhang, Weili Fu
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引用次数: 0
Large scale, high purity, high quality isolation of mesenchymal stem cells from osteo-organoids. 从骨组织中大规模、高纯度、高质量地分离间充质干细胞。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.008
Yan Xu, Fuxin Wei
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引用次数: 0
Membrane-coated nanoparticles as a biomimetic targeted delivery system for tumour therapy. 膜包纳米粒子作为肿瘤治疗的生物仿生靶向传输系统。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.004
Haoyu Guo, Mingke Guo, Zhidao Xia, Zengwu Shao

Drug therapy towards tumours often causes adverse effects because of their non-specific nature. Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery. By camouflaging the nanoparticles with natural derived or artificially modified cell membranes, the nano-payloads are bestowed with properties from cell membranes such as longer circulation, tumour or inflammation-targeting, immune stimulation, augmenting the performance of traditional therapeutics. In this review, we review the development of membrane coating technology, and summarise the technical details, physicochemical properties, and research status of membrane-coated nanoparticles from different sources in tumour treatment. Finally, we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use. Taken together, membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.

由于药物的非特异性,对肿瘤的药物治疗往往会产生不良反应。膜包覆技术和膜包覆纳米粒子为靶向安全给药提供了一个先进而有前景的平台。通过用天然衍生或人工修饰的细胞膜伪装纳米颗粒,纳米载荷被赋予了细胞膜的特性,如更长的循环时间、肿瘤或炎症靶向性、免疫刺激,从而增强了传统疗法的性能。在这篇综述中,我们回顾了膜包衣技术的发展,总结了不同来源的膜包衣纳米粒子在肿瘤治疗中的技术细节、理化性质和研究现状。最后,我们还展望了将膜包衣技术从实验转化为临床应用的前景和挑战。综上所述,膜包衣纳米粒子必将成为未来最具潜力的抗肿瘤策略之一。
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引用次数: 0
Exploring the potential of micro-nano composite structures for COVID-19 vaccines and beyond. 探索用于 COVID-19 疫苗及其他疫苗的微纳米复合结构的潜力。
Pub Date : 2024-03-28 eCollection Date: 2024-01-01 DOI: 10.12336/biomatertransl.2024.01.009
Danli Cui, Yiting Lei
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引用次数: 0
期刊
Biomaterials Translational
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