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Exosomes in Intervertebral Disc Regeneration: Roles, Opportunities, and Challenges 外泌体在椎间盘再生中的作用、机遇和挑战
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-21 DOI: 10.1002/anbr.202500074
Xianglong Zhou, Tianyi Xia, Jiheng Xiao, Jianhui Xiang, Hanhong Fang, Haoran Zhou, Yiqiang Hu, Liming Xiong

Intervertebral disc degeneration (IVDD), a major cause of low back pain, poses significant global health and socioeconomic challenges. Current therapies have limited effectiveness in reversing degeneration, which underscores the need for advanced treatment strategies. Exosomes, which are nanoscale extracellular vesicles, have emerged as promising therapeutic agents for IVDD due to their unique biological properties. They exert their effects through multiple mechanisms, such as regulating the extracellular matrix, promoting cell proliferation, and exerting anti-inflammatory effects. This review summarizes recent advances in exosome-based therapies for IVDD. It encompasses their mechanisms, cell sources, engineering technologies, and progress in clinical translation. Additionally, the challenges and opportunities related to their future clinical application are discussed, and their potential to revolutionize the treatment of IVDD is highlighted.

椎间盘退变(IVDD)是腰痛的一个主要原因,对全球健康和社会经济构成重大挑战。目前的治疗方法在逆转退行性变方面效果有限,这强调了需要先进的治疗策略。外泌体是一种纳米级的细胞外囊泡,由于其独特的生物学特性,已成为治疗IVDD的有希望的药物。它们通过调节细胞外基质、促进细胞增殖、发挥抗炎作用等多种机制发挥作用。本文综述了体外泌体治疗IVDD的最新进展。它包括它们的机制、细胞来源、工程技术和临床翻译的进展。此外,讨论了与它们未来临床应用相关的挑战和机遇,并强调了它们革新IVDD治疗的潜力。
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引用次数: 0
Nanostructured Biomaterial-Based Approaches to Support Induced Pluripotent Stem Cell Differentiation 纳米结构生物材料支持诱导多能干细胞分化的方法
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-21 DOI: 10.1002/anbr.202500072
Beatriz A. B. R. Passos, Matteo Battaglini, Gianni Ciofani

The possibility to control the proliferation of stem cells and guide their differentiation toward specific cellular lineages holds great promise as a potential therapeutic approach for regenerating and substituting damaged tissues, and in the treatment of several human diseases. In recent years, developing strategies for obtaining induced pluripotent stem cells (iPSCs) from adult tissues has been a groundbreaking scientific discovery; the rationale behind the exploitation of iPSCs in therapy consists in the isolation of adult cells, their reprogramming into iPSCs, and the subsequent differentiation into somatic cells. However, traditional differentiation procedures usually cannot finely tune and control the differentiation of iPSCs, leading to undesired cellular subpopulations and potentially adverse effects in the case of cellular grafting in adult tissues. In this context, nanostructured biomaterial-based approaches for the guided differentiation of iPSCs represent a promising tool for overcoming the limitations of traditional protocols. This review aims to provide the current state of the art concerning the exploitation of nanostructured biomaterials (scaffolds or nanocarriers) to control and tune the differentiation processes of iPSCs. With this work, it is hoped to provide new insights and perspectives into biomaterial designing and application strategies in the context of iPSC-based studies.

控制干细胞增殖并引导其向特定细胞谱系分化的可能性,作为再生和替代受损组织以及治疗几种人类疾病的潜在治疗方法,具有很大的前景。近年来,开发从成人组织中获得诱导多能干细胞(iPSCs)的策略是一项突破性的科学发现;利用多能干细胞进行治疗的基本原理是分离成体细胞,将其重新编程为多能干细胞,然后分化为体细胞。然而,传统的分化过程通常不能很好地调节和控制iPSCs的分化,导致不希望的细胞亚群和潜在的不利影响,在成人组织的细胞移植的情况下。在这种情况下,基于纳米结构生物材料的诱导多能干细胞分化方法是克服传统方法局限性的一种很有前途的工具。本文综述了利用纳米结构生物材料(支架或纳米载体)控制和调节iPSCs分化过程的最新研究进展。希望通过这项工作,为ipsc研究背景下的生物材料设计和应用策略提供新的见解和视角。
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引用次数: 0
Cationic Nanoparticles Mitigate Chemotherapy-Induced Peripheral Neuropathy 阳离子纳米颗粒减轻化疗诱导的周围神经病变
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-16 DOI: 10.1002/anbr.202500002
Divya Bhansali, Rocco Latorre, Raquel Tonello, David Poolman, Suwan Ding, Brian L. Schmidt, Nigel W. Bunnett, Kam W. Leong

Chemotherapy-induced peripheral neuropathy (CIPN) is a major clinical challenge, particularly for patients treated with paclitaxel (PTX), a highly effective yet neurotoxic chemotherapeutic agent. PTX often causes debilitating neuropathic pain, including mechanical and cold allodynia, driven by neuroinflammation and altered peripheral neuron excitability. This study investigates PTX-loaded cationic PAMAM-Chol nanoparticles (PTX NPs) as a novel strategy to mitigate CIPN. PTX NPs exhibit high drug loading efficiency (99%), sustained release, and reduced neurotoxicity in neuronal cell models. In a murine CIPN model, PTX NPs produce an 85% overall reduction in cold allodynia with a peak inhibition of 90% at day 8 and accelerate the recovery of mechanical allodynia, restoring withdrawal thresholds to baseline levels by day 14, compared to persistent nociception with unencapsulated PTX. PTX NPs also suppress dorsal root ganglia inflammation, reducing the expression of proinflammatory cytokines TNFα and IL-1β. Furthermore, as indicated by phosphorylated ERK, neuronal activation is prevented in PTX NP-treated mice, suggesting a reduction in central sensitization. Importantly, PTX NPs demonstrate no observable toxicity in liver or kidney function. These findings establish a proof of concept that nanomedicine-mediated delivery can alleviate CIPN effectively, offering a promising approach to refine PTX-based chemotherapy regimens.

化疗引起的周围神经病变(CIPN)是一个主要的临床挑战,特别是对于使用紫杉醇(PTX)治疗的患者,紫杉醇是一种高效但具有神经毒性的化疗药物。PTX常引起衰弱性神经性疼痛,包括机械性和冷性异常性疼痛,由神经炎症和周围神经元兴奋性改变引起。本研究研究了PTX负载的阳离子PAMAM-Chol纳米颗粒(PTX NPs)作为减轻CIPN的新策略。PTX NPs在神经元细胞模型中表现出高的载药效率(99%)、缓释和降低的神经毒性。在小鼠CIPN模型中,与未包封PTX的持续伤害相比,PTX NPs在第8天使冷异常性疼痛总体减少85%,峰值抑制率为90%,并加速机械异常性疼痛的恢复,在第14天将戒断阈值恢复到基线水平。PTX NPs还能抑制背根神经节炎症,降低促炎细胞因子TNFα和IL-1β的表达。此外,正如磷酸化的ERK所示,PTX np处理小鼠的神经元激活被阻止,表明中枢致敏性降低。重要的是,PTX NPs对肝脏或肾脏功能没有明显的毒性。这些发现证明了纳米药物介导的递送可以有效缓解CIPN的概念,为改进基于ptx的化疗方案提供了一种有希望的方法。
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引用次数: 0
Reshaping Protein-Based Nanoparticles: Innovative Artificial Intelligence-Driven Strategies for Structural Design and Applications 重塑蛋白质纳米颗粒:结构设计和应用的创新人工智能驱动策略
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-05 DOI: 10.1002/anbr.202500017
Mohammad Mahmoudi Gomari, Mehdi Alidadi, Neda Rostami, Sidi A. Bencherif

Nanoparticles (NPs) have become a pivotal technology in biomedical research due to their unique physicochemical properties and nanoscale size, allowing for targeted applications. Among NP materials, proteins and their derivatives stand out for their biocompatibility, engineering flexibility, and inherent biological functions, making them especially attractive for NP design. However, the structural and biochemical complexity of proteins has historically presented challenges in NP development. Recent advancements in artificial intelligence (AI) have transformed this field. Neural network models such as AlphaFold, ProteinMPNN, and RoseTTAFold, along with protein language models like evolutionary scale modeling, enable the design of protein-based NPs (PNPs) with diverse symmetries, shapes, and functionalities. These AI-driven approaches address traditional limitations, unlocking new possibilities in nanomedicine. This review explores the transformative role of AI in PNP design, emphasizing its potential to broaden applications, solve challenges, and drive innovative solutions in biotechnology and medical research.

纳米粒子(NPs)由于其独特的物理化学性质和纳米级尺寸,使其具有针对性的应用,已成为生物医学研究中的关键技术。在NP材料中,蛋白质及其衍生物因其生物相容性、工程灵活性和内在的生物功能而脱颖而出,这使得它们对NP设计特别有吸引力。然而,蛋白质的结构和生化复杂性一直是NP发展的挑战。人工智能(AI)的最新进展已经改变了这一领域。神经网络模型(如AlphaFold、ProteinMPNN和RoseTTAFold)以及蛋白质语言模型(如进化尺度建模)使基于蛋白质的NPs (PNPs)具有不同的对称性、形状和功能。这些人工智能驱动的方法解决了传统的局限性,为纳米医学开辟了新的可能性。本文探讨了人工智能在PNP设计中的变革性作用,强调了其在生物技术和医学研究中扩大应用、解决挑战和推动创新解决方案的潜力。
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引用次数: 0
Magnetic Multifunctional Nanoparticles for Effective Targeted Cancer Therapy 磁性多功能纳米颗粒有效靶向治疗癌症
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-04 DOI: 10.1002/anbr.202400176
Yao Miao, Qing Bao, Tao Yang, Mingying Yang, Chuanbin Mao

Due to the lack of targeting specificity, rapid clearance, and high toxicity associated with small molecule drugs in tumor treatment, the design of an effective drug delivery system is crucial. To better overcome physiological barriers and achieve prolonged tumor retention, nanoparticles (Fe3O4@SiO2@Au, termed FSA-NPs), made of core–shell NPs (Fe3O4@SiO2), consisting of a Fe3O4 core and a mesoporous silica (SiO2) shell, and with their surfaces decorated with gold NPs, are constructed. The FSA-NPs have a size range of 60–80 nm and a mildly negative surface charge. The magnetic Fe3O4 core imparts magnetic targeting capabilities to FSA-NPs, while the high porosity of the mesoporous silica shell enables efficient drug loading. Additionally, the gold NPs can convert light into heat. As a result, after being internalized by A549 lung cancer cells, FSA-NPs exhibit potent cytotoxic effects against the cancer cells under an applied magnetic field, making them a promising theranostic agent for integrated cancer diagnosis and therapy.

由于小分子药物在肿瘤治疗中缺乏靶向特异性、快速清除率和高毒性,设计有效的给药系统至关重要。为了更好地克服生理障碍并延长肿瘤滞留时间,纳米颗粒(Fe3O4@SiO2@Au,称为FSA-NPs)由核-壳NPs (Fe3O4@SiO2)制成,由Fe3O4核和介孔二氧化硅(SiO2)壳组成,表面装饰有金NPs。FSA-NPs的尺寸范围为60-80 nm,表面带轻微的负电荷。磁性Fe3O4核赋予了FSA-NPs磁性靶向能力,而介孔二氧化硅壳的高孔隙率使其能够高效装载药物。此外,金纳米粒子可以将光转化为热。因此,FSA-NPs被A549肺癌细胞内化后,在外加磁场作用下对癌细胞表现出强大的细胞毒作用,是一种很有前景的癌症综合诊断和治疗药物。
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引用次数: 0
Bioprinting-Assisted Tissue Assembly to Investigate Endothelial Cell Contributions in Cardiac Fibrosis and Focal Fibrosis Modeling 生物打印辅助组织组装研究内皮细胞在心脏纤维化和局灶性纤维化模型中的作用
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-02 DOI: 10.1002/anbr.202400148
Dong Gyu Hwang, Hwanyong Choi, Myungji Kim, Minji Kim, Donghwan Kim, Jinseon Park, Jinah Jang

Cardiac fibrosis is characterized by excessive extracellular matrix (ECM) deposition, driven by the activation of cardiac fibroblasts (cFBs) and endothelial-to-mesenchymal transition (EndMT). Endothelial cells (ECs) contribute to cardiac fibrosis through EndMT, transforming into myofibroblasts that promote fibrosis, while also playing a regulatory role through signaling pathways, such as PI3K-Akt and Notch. In this article, engineered heart tissue models, composed of cardiomyocytes and cFBs (CMF) and vascularized model incorporating ECs (CMFE) tissues is created to investigate the role of ECs in transforming growth factor-β (TGF-β)-induced cardiac fibrosis. Prior to fibrosis induction, CMFE exhibits enhanced activation of fibrosis-related signaling, endothelial integrity pathways, and PI3K-Akt and Notch signaling compared to CMF. Following TGF-β treatment, CMF exhibits typical fibrotic features, including increased ECM deposition, tissue stiffening, and reduced contractility. In contrast, the CMFE demonstrates attenuated fibrotic responses, maintaining tissue mechanics and contractile function. Gene expression and histology reveals both fibrotic and protective processes in CMFE. Moreover, the bioprinting-assisted tissue assembly (BATA) approach enable focal fibrosis modeling, revealing that fibrotic regions disrupted calcium propagation and induced electrophysiological abnormalities. These findings highlight BATA as a promising platform for studying cardiac fibrosis and developing targeted therapeutic strategies.

心脏纤维化的特征是过度的细胞外基质(ECM)沉积,由心脏成纤维细胞(cfb)的激活和内皮到间质转化(EndMT)驱动。内皮细胞(ECs)通过EndMT参与心脏纤维化,转化为促进纤维化的肌成纤维细胞,同时也通过PI3K-Akt和Notch等信号通路发挥调节作用。本文建立了由心肌细胞和cfb (CMF)组成的工程化心脏组织模型和含有ECs (CMFE)组织的血管化模型,以研究ECs在转化生长因子-β (TGF-β)诱导的心脏纤维化中的作用。在纤维化诱导之前,与CMF相比,CMFE表现出增强的纤维化相关信号、内皮完整性通路、PI3K-Akt和Notch信号的激活。TGF-β治疗后,CMF表现出典型的纤维化特征,包括ECM沉积增加、组织硬化和收缩性降低。相比之下,CMFE表现出减弱的纤维化反应,维持组织力学和收缩功能。基因表达和组织学揭示了CMFE的纤维化和保护过程。此外,生物打印辅助组织组装(BATA)方法可以实现局灶性纤维化建模,揭示纤维化区域破坏钙增殖并诱导电生理异常。这些发现突出了BATA作为研究心脏纤维化和开发靶向治疗策略的一个有前途的平台。
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引用次数: 0
Time-of-Flight Secondary Ion Mass Spectrometry-Partial Least Square Regression for Quantifying Interleukin-8 in Biopolymer Matrices 飞行时间二次离子质谱-偏最小二乘回归定量生物聚合物基质中白细胞介素-8
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-02 DOI: 10.1002/anbr.202500066
Ralf Zimmermann, Mirko Nitschke, Marten Samulowitz, Nicholas R. Dennison, Carsten Werner

Unraveling the complexity of biomatrices is a persisting challenge in many areas of the life sciences. The detection of soluble signaling molecules—cytokines and growth factors—within multicomponent biopolymer scaffolds is of particular interest as they control important biological processes such as the development of tissues, pathologies, and regeneration. The application of time-of-flight secondary ion mass spectrometry (ToF-SIMS) for the detection of interleukin-8 (IL-8), a chemokine involved in inflammation and cancer, is explored within biopolymer matrices of different complexity. To establish the workflow, IL-8 is embedded with graded mass fractions in thin biopolymer matrices consisting of heparin and/or bovine serum albumin, followed by a comprehensive ToF-SIMS analysis of the prepared samples. Partial least square regression models are developed and successfully applied to detect IL-8 mass fractions down to 1 ppm on the basis of the measured ToF-SIMS spectra. The methodology is successfully applied to detect IL-8 in Matrigel and poly(ethylene glycol)-heparin matrices with similar sensitivity. Given the high performance of state-of-the-art SIMS instruments and the increasing power of machine learning algorithms, it is envisioned that the established approach, in combination with other methods, will enable a comprehensive assessment of soluble signaling molecules in (engineered) matrix-supported 3D cell and organoid cultures.

在生命科学的许多领域,揭示生物基质的复杂性是一个持续的挑战。可溶性信号分子——细胞因子和生长因子——在多组分生物聚合物支架中的检测是特别感兴趣的,因为它们控制着重要的生物过程,如组织的发育、病理和再生。应用飞行时间二次离子质谱法(ToF-SIMS)检测白细胞介素-8 (IL-8),一种参与炎症和癌症的趋化因子,在不同复杂性的生物聚合物基质中进行了探索。为了建立工作流程,将IL-8用分级质量分数嵌入由肝素和/或牛血清白蛋白组成的薄生物聚合物基质中,然后对制备的样品进行全面的ToF-SIMS分析。开发了偏最小二乘回归模型,并成功地应用于检测IL-8质量分数低至1ppm的基础上测量的ToF-SIMS光谱。该方法成功地用于检测基质和聚乙二醇-肝素基质中的IL-8,具有相似的灵敏度。考虑到最先进的SIMS仪器的高性能和机器学习算法的不断增强的能力,设想建立的方法与其他方法相结合,将能够全面评估(工程)基质支持的3D细胞和类器官培养中的可溶性信号分子。
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引用次数: 0
Advances on Albumin-Based Carriers for Anticancer Drug Delivery 基于白蛋白的抗癌药物载体研究进展
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-06-01 DOI: 10.1002/anbr.202500011
Ruoli Zhou, Rongbin Zhong, Zhonghui Luo, Hua Wei, Cui-Yun Yu

Albumin is the most abundant protein in plasma, featuring a unique chemical structure and conformation that underpins its functions. Its excellent biocompatibility, nontoxicity and non-immunogenicity make it an ideal carrier for encapsulating therapeutic agents, particularly in controlled release applications for cancer treatment. Although existing reviews focus on albumin-based particulate delivery systems, there is a lack of comprehensive analysis from the perspective of using albumin's structural characteristics and binding sites for drug delivery. This review categorizes albumin's drug-loading modes based on its surface-active groups and internal binding sites, emphasizing drug-loading strategies and targeting mechanisms. It also details the preparation and modification methods for albumin nanoparticles, along with clinical performance evaluations. Finally, it addresses current challenges and proposes potential solutions. This review aims to provide valuable insights for developing advanced albumin-based anticancer drugs with enhanced therapeutic efficacy.

白蛋白是血浆中最丰富的蛋白质,具有独特的化学结构和构象,支撑着它的功能。其优良的生物相容性、无毒性和非免疫原性使其成为包封治疗药物的理想载体,特别是在癌症治疗的控释应用中。虽然现有的综述主要集中在基于白蛋白的颗粒递送系统上,但缺乏从利用白蛋白的结构特征和结合位点进行药物递送的角度进行全面分析。本文根据白蛋白的表面活性基团和内部结合位点对其载药方式进行了分类,重点介绍了载药策略和靶向机制。它还详细介绍了白蛋白纳米颗粒的制备和修饰方法,以及临床性能评估。最后,阐述了当前的挑战并提出了潜在的解决方案。本文旨在为开发以白蛋白为基础的晚期抗癌药物提供有价值的见解。
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引用次数: 0
Laser-Patterned Diamond Electrodes for Adhesion and Proliferation of Human Mesenchymal Stem Cells 激光图纹金刚石电极用于人间充质干细胞的粘附和增殖
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-05-27 DOI: 10.1002/anbr.202500041
Hassan N. Al Hashem, Kaiwen Zhang, Amanda N. Abraham, Deepak Sharma, Andre Chambers, Mehrnoosh Moghaddar, Chayla L. Reeves, Sanjay K. Srivastava, Amy Gelmi, Arman Ahnood

The ability to form diamond electrodes on insulating polycrystalline diamond substrates using single-step laser patterning and the use of these electrodes as a substrate that supports the adhesion and proliferation of human mesenchymal stem cells (hMSCs) are demonstrated. Laser-induced graphitization results in a conductive amorphous carbon surface, rich in oxygen- and nitrogen-terminated groups. This leads to an electrode with a high specific capacitance of 182 μF cm2, a wide water window of 3.25 V, and a low electrochemical impedance of 129 Ω cm2 at 1 kHz—essential attributes for effective bioelectronic cell interfaces. The electrode's surface exhibits no cytotoxic responses with hMSCs, supporting cell adhesion and proliferation. Cells cultured on the electrode display significant elongation and alignment along the direction of the laser-patterned microgrooves—an additional modality for cellular modulation. The combination of favorable electrochemical performance and effective cellular control makes laser-patterned diamond electrodes a versatile platform in stem cell therapeutics. This direct fabrication approach paves the way for the integration of diamond electrodes in bioelectronic devices, offering new opportunities for tissue engineering and electroactive biomaterial applications.

利用单步激光图像化技术在绝缘多晶金刚石衬底上形成金刚石电极,并将这些电极用作支持人间充质干细胞(hMSCs)粘附和增殖的衬底。激光诱导石墨化产生导电的无定形碳表面,富含氧端基和氮端基。这使得电极具有182 μF cm2的高比电容、3.25 V的宽水窗和1khz时129 Ω cm2的低电化学阻抗——这是有效的生物电子细胞界面的基本属性。电极表面对hMSCs无细胞毒性反应,支持细胞粘附和增殖。在电极上培养的细胞显示出沿激光图案微凹槽方向的显着伸长和排列-这是细胞调制的另一种方式。良好的电化学性能和有效的细胞控制相结合,使激光图案金刚石电极在干细胞治疗中成为一个通用的平台。这种直接制造方法为金刚石电极在生物电子器件中的集成铺平了道路,为组织工程和电活性生物材料的应用提供了新的机会。
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引用次数: 0
Correction to “Bioreactors: A Regenerative Approach to Skeletal Muscle Engineering for Repair and Replacement” 对“生物反应器:骨骼肌修复和替代工程的再生方法”的更正
IF 4.4 Q2 ENGINEERING, BIOMEDICAL Pub Date : 2025-05-27 DOI: 10.1002/anbr.202500111

Williamson, A., Khoshmanesh, K., Pirogova, E., Yang, P., Snow, F., Williams, R., Quigley, A. and Kapsa, R.M.I. (2024), Bioreactors: A Regenerative Approach to Skeletal Muscle Engineering for Repair and Replacement. Adv. NanoBiomed Res., 4: 2400030. https://doi.org/10.1002/anbr.202400030

Correction to “Table 1. Myogenic Markers”

Table 1, in paragraph 7 of the “Introduction” section, the text “Initiates differentiation of myoblasts to stem cells” was incorrect for myogenic factors Myf5 and MyoD. This should have read: “Initiates differentiation of stem cells to myoblasts.”

We apologize for this error.

Williamson, A., Khoshmanesh, K., Pirogova, E., Yang, P., Snow, F., Williams, R., Quigley, A.和Kapsa, R.M.I.(2024),生物反应器:骨骼肌修复和替代工程的再生方法。纳米生物学报,4(4):2400030。https://doi.org/10.1002/anbr.202400030Correction到表1。表1,“引言”部分第7段中,文本“initiate differentiation of myoblasts to stem cells”对于Myf5和MyoD的成肌因子是不正确的。这应该是:“启动干细胞向成肌细胞的分化。”我们为这个错误道歉。
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引用次数: 0
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