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Three-dimensional tissue engineering and organoid technologies for retinal regeneration and therapy 三维组织工程和类器官技术用于视网膜再生和治疗
IF 5.7 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-14 DOI: 10.1002/btm2.70051
Yiqi Wang, Douglas Jiang, Qinglong Wang, Yun Cao, Hong Guo, Yi Lu, Feng Tian

The human eye, a masterpiece of evolution, orchestrates the intricate process of vision. The retina is a tissue with a layered structure that plays a critical role in converting light signals into neural impulses interpretable by the brain. Various eye conditions such as glaucoma, retinitis pigmentosa, age-related macular degeneration, and other retinopathies are characterized by damage or degeneration in the retina. Recent strides in organoid cultivation and advanced three-dimensional (3D) bioengineering technologies offer promising avenues for potential therapeutic interventions. Compared to traditional two-dimensional cell culture models, which are non-natural and limited in accuracy, 3D models, including organoids, electrospinning constructs, microfabrication-based scaffolds, and hydrogel systems, are more delicate, especially in recapitulating tissue architecture, offering spatial patterning, and enabling vascularization. Retinal organoids are 3D multicellular structures derived from stem cells that can mimic the retina's layered architecture and functionality. However, their inherent complexity, including the presence of multiple differentiated cell types, may not be necessary for all disease modeling applications. In contrast, engineered 3D technologies can be tailored to specific retinal diseases by incorporating only the most relevant cell types, matrix stiffness, and spatial arrangements, offering greater experimental control and reproducibility in targeted therapeutic testing. In the following paper, we will discuss organoid generation in detail. Besides retinal organoids, bioprinting is another promising avenue for regenerative medicines. We further review a suite of 3D fabrication strategies, including inkjet and laser-assisted bioprinting, electrospun scaffolds, and hydrogel systems, and evaluate their current and potential applications in modeling retinal diseases and developing translational therapies. We will also delve into the contemporary advancements in retinal therapies, particularly emphasizing the roles and prospects of organoid and engineered 3D technologies.

人类的眼睛是进化的杰作,它协调了复杂的视觉过程。视网膜是一种具有分层结构的组织,在将光信号转化为大脑可理解的神经脉冲方面起着至关重要的作用。各种眼病,如青光眼、视网膜色素变性、年龄相关性黄斑变性和其他视网膜病变,都以视网膜损伤或变性为特征。类器官培养和先进的三维(3D)生物工程技术的最新进展为潜在的治疗干预提供了有希望的途径。与传统的二维细胞培养模型相比,三维模型,包括类器官、静电纺丝结构、基于微结构的支架和水凝胶系统,更加精细,特别是在再现组织结构、提供空间图案和实现血管化方面。视网膜类器官是由干细胞衍生的三维多细胞结构,可以模仿视网膜的分层结构和功能。然而,它们固有的复杂性,包括多种分化细胞类型的存在,可能不是所有疾病建模应用所必需的。相比之下,工程3D技术可以通过仅结合最相关的细胞类型、基质刚度和空间排列来针对特定的视网膜疾病进行定制,从而在靶向治疗测试中提供更好的实验控制和可重复性。在下面的文章中,我们将详细讨论类器官的产生。除了视网膜类器官,生物打印是再生药物的另一个有前途的途径。我们进一步回顾了一系列3D制造策略,包括喷墨和激光辅助生物打印、电纺丝支架和水凝胶系统,并评估了它们在视网膜疾病建模和开发转化治疗方面的当前和潜在应用。我们还将深入研究视网膜治疗的当代进展,特别强调类器官和工程3D技术的作用和前景。
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引用次数: 0
Advanced hydrogel therapeutics for intervertebral disc degeneration: Engineering structural–functional properties in natural and synthetic biomaterials 先进的水凝胶治疗椎间盘退变:天然和合成生物材料的工程结构功能特性
IF 5.7 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-11 DOI: 10.1002/btm2.70059
Tao Chen, Dading Lu, Siqiao Wang, Huiyi Yang, Wenyong Fan, Zhihui Xiao, Zhaojie Wang, Pooyan Makvandi, Rongrong Zhu, Liming Cheng

Low back pain is a global health challenge, imposing substantial socioeconomic burdens. Intervertebral disc degeneration (IVDD) is a leading cause of low back pain and can lead to further spinal complications. Current treatments for IVDD are limited to conservative measures and surgery, lacking curative options. Advances in biomaterials science and regenerative medicine have introduced bioactive hydrogels as promising treatments for IVDD. This review summarizes the physiology of the intervertebral disc, the pathophysiology of IVDD, existing diagnostic methods, and current treatment strategies. Importantly, this review examines recent advances in hydrogel treatments for IVDD, emphasizing the biological and material properties of various hydrogels. It compares the advantages and limitations of natural and synthetic hydrogels, outlining the classification of hydrogel delivery substances. Lastly, it identifies current challenges and suggests future research directions to optimize the application of bioactive materials in IVDD treatment.

腰痛是一个全球性的健康挑战,造成了巨大的社会经济负担。椎间盘退变(IVDD)是腰痛的主要原因,并可导致进一步的脊柱并发症。目前IVDD的治疗仅限于保守措施和手术,缺乏治愈的选择。生物材料科学和再生医学的进步已经引入了生物活性水凝胶作为IVDD的有希望的治疗方法。本文综述了椎间盘的生理学、IVDD的病理生理学、现有的诊断方法和目前的治疗策略。重要的是,本文综述了水凝胶治疗IVDD的最新进展,强调了各种水凝胶的生物学和材料特性。比较了天然水凝胶和合成水凝胶的优点和局限性,概述了水凝胶输送物质的分类。最后,提出了优化生物活性材料在IVDD治疗中的应用所面临的挑战和未来的研究方向。
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引用次数: 0
3D printed nerve guidance conduit for biologics-free nerve regeneration and vascular integration 3D打印神经引导导管用于无生物制剂的神经再生和血管整合
IF 5.7 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-04 DOI: 10.1002/btm2.70057
Jacob Schimelman, David B. Berry, Susie Johnson, Zhitian Ruskin Shi, Sophie Brown, Quyen T. Nguyen, Shaochen Chen

There is a clinical need for an effective nerve guidance conduit to treat peripheral nerve injuries. Many studies have explored different materials and active cues to guide neural regeneration, with some success. However, none have demonstrated a comparable or better functional recovery than the clinical standard autograft. Autografts are often insufficient for reconstruction of an injury to long nerves such as the sciatic or brachial plexus. Synthetic nerve guidance conduits (NGCs) have been investigated for these injuries to guide axonal regeneration and lead to functional recovery. We have designed a biologics-free hydrogel-based multi-channel conduit with defined microscale features to guide axonal outgrowth. To investigate extraneural vascular infiltration and its effects on functional recovery, we also designed a multi-microchannel conduit with defined regularly spaced micropores, orthogonal to the axon guidance channels. Using our custom-built Rapid Projection, Image-guided, Dynamic (RaPID) bioprinting system, we were able to fabricate each hydrogel conduit within minutes from a milliliter-volume prepolymer vat. With our state-of-the-art printing platform, we have achieved NGCs with a consistent channel wall width of 10 μm. We implanted the NGCs for 17 weeks in a murine sciatic nerve transection injury model. We assessed the functional recovery by dynamic gait analysis throughout the recovery period and by compound muscle action potential (CMAP) electrophysiology before NGC harvesting. Both the non-porous and micro-porous conduit groups led to functional nerve regeneration on par with the autograft group. Further, both conduit groups resulted in restoration of bulk motor function to pre-injury performance.

临床需要一种有效的神经引导导管来治疗周围神经损伤。许多研究探索了不同的材料和主动线索来指导神经再生,并取得了一些成功。然而,没有一种表现出与临床标准自体移植物相当或更好的功能恢复。自体移植物通常不足以重建长神经损伤,如坐骨神经或臂丛神经。人工神经引导导管(NGCs)已被研究用于指导这些损伤的轴突再生和功能恢复。我们设计了一种不含生物制剂的基于水凝胶的多通道导管,具有明确的微尺度特征,以引导轴突的生长。为了研究神经外血管浸润及其对功能恢复的影响,我们还设计了一个与轴突引导通道正交的多微通道导管。使用我们定制的快速投影、图像引导、动态(Rapid)生物打印系统,我们能够在几分钟内从一个毫升体积的预聚体大桶中制造出每个水凝胶导管。凭借我们最先进的打印平台,我们已经实现了通道壁宽为10 μm的NGCs。我们将NGCs植入小鼠坐骨神经横断损伤模型17周。我们通过动态步态分析和复合肌肉动作电位(CMAP)电生理分析来评估整个恢复期间的功能恢复。无孔和微孔导管组的神经功能再生与自体移植物组相当。此外,两组导管均可使大容量运动功能恢复到损伤前的水平。
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引用次数: 0
Multi‐modal screening for synergistic neuroprotection of mild extremely preterm brain injury 轻度极早产儿脑损伤协同神经保护的多模式筛选
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-02 DOI: 10.1002/btm2.70058
Zheyu Ruby Jin, Kylie A. Corry, Olivia C. Brandon, Matthew J. Magoon, Hawley Helmbrecht, Daniel H. Moralejo, Robell Bassett, Sarah E. Kolnik, Patrick M. Boyle, Sandra E. Juul, Elizabeth A. Nance, Thomas R. Wood
Preterm brain injury affects both white and gray matter, including altered cortical development and gyrification, with associated neurodevelopmental sequelae such as cerebral palsy and learning deficits. The preterm brain also displays regionally heterogeneous responses to both injury and treatment, suggesting that drug combinations may be needed to provide global neuroprotection. We developed an extremely preterm‐equivalent organotypic whole hemisphere (OWH) slice culture mild injury model using the gyrencephalic ferret brain to probe treatment mechanisms of promising therapeutic agents and their combination. Regional and global responses to injury and treatment were assessed by cell death quantification, machine learning‐augmented morphological microglia assessments, and digital transcriptomics. Using two promising therapeutic agents, azithromycin (Az) and erythropoietin (Epo), we show minimal neuroprotection by either therapy alone, but evidence of synergistic neuroprotection by Az*Epo both globally and regionally. This effect of Az*Epo involved augmentation of transcriptomic responses to injury related to neurogenesis and neuroplasticity and downregulation of transcripts involved in cytokine production, inflammation, and cell death. With the increasing need to develop therapies for extremely preterm brain injury, the ferret OWH slice culture model provides a high‐throughput platform to examine combinations of therapeutics as part of a preclinical therapeutic pipeline.
早产儿脑损伤会影响白质和灰质,包括皮质发育改变和脑回化,并伴有相关的神经发育后遗症,如脑瘫和学习障碍。早产儿的大脑也对损伤和治疗表现出区域异质性反应,这表明可能需要药物联合来提供全局神经保护。我们建立了一种极早产等效器官型全半球(OWH)切片培养的雪貂脑轻度损伤模型,以探讨有前景的治疗药物及其联合治疗的机制。通过细胞死亡量化、机器学习增强形态学小胶质细胞评估和数字转录组学评估对损伤和治疗的区域和整体反应。使用两种有前景的治疗药物,阿奇霉素(Az)和促红细胞生成素(Epo),我们显示单独治疗的神经保护作用很小,但azo *Epo在全球和区域都有协同神经保护的证据。Az*Epo的作用包括增强与神经发生和神经可塑性相关的损伤的转录组反应,以及下调与细胞因子产生、炎症和细胞死亡有关的转录。随着对极早产儿脑损伤治疗方法的需求不断增加,雪貂OWH切片培养模型提供了一个高通量的平台,可以作为临床前治疗管道的一部分来检查治疗方法的组合。
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引用次数: 0
Correction to “Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease” 更正“大分子纳米颗粒减轻活性氧和炎症损伤治疗阿尔茨海默病”
IF 5.7 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-08-01 DOI: 10.1002/btm2.70052

Zhang B, Zhao Y, Guo K, et al. Macromolecular nanoparticles to attenuate both reactive oxygen species and inflammatory damage for treating Alzheimer's disease. Bioeng Transl Med. 2023;8(3):e10459.

In the DAPI channel of figure 3g. The pictures above and below have been reversed. This is incorrect. The correct pictures should be reordered.

We apologize for this error.

张斌,赵毅,郭凯,等。大分子纳米粒子减弱活性氧和炎症损伤治疗阿尔茨海默病。中国生物医学工程学报,2009;8(3):10459。在图3g的DAPI通道中。上面和下面的图片是颠倒的。这是不正确的。正确的图片需要重新订购。我们为这个错误道歉。
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引用次数: 0
Decellularized lymph node scaffolds accelerate restoration of lymphatic drainage in rat hind limb lymphedema 脱细胞淋巴结支架加速大鼠后肢淋巴水肿淋巴引流的恢复
IF 5.7 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-07-31 DOI: 10.1002/btm2.70056
Yang Jian, Jian Zhou, Wenjie Pan, Jiayin Chen, Yanji Zhang, Yanqi Li, Xin Liu, Shune Xiao, Chenliang Deng, Zairong Wei

Background

There is a lack of effective lymphedema prevention methods. The objective of this study was to investigate the ability of decellularized lymph nodes (dLNs) transplantation to prevent hindlimb lymphedema.

Methods

Porcine dLNs were prepared using 1% sodium dodecyl sulfate and 1% Triton X-100, and the effectiveness of decellularization was assessed by histological assessment and DNA quantification. Lymph node (LN) fragments and dLNs were transplanted into mice, and samples were collected for evaluating biocompatibility at the fourth week postsurgery. Thirty-six SD rats were separated into a control group (lymphatic dissection), a dLNs group (lymphatic dissection and dLNs transplant) and a sham group (inguinal skin circumferentially incised). Hindlimb circumference was monitored every 3 days. Indocyanine green lymphography was performed before and every week after surgery. Samples were collected for histological assessment at the second and fourth weeks.

Results

The dLNs showed virtually complete absence of cellular material, maintenance of spatial structures, and good biocompatibility and induced immune cell infiltration. Compared with that of the control group, the average hindlimb circumference of the dLN group was significantly reduced on postoperative days (PODs) 8, 12, and 16, and that of the sham group was significantly reduced on PODs 4, 8, 12, 16, and 20. The sham group exhibited intact inguinal LNs and lymphatic drainage. Neonatal lymphatic vessels (LVs) were observed in the dLN group, and obvious dermal backflow was observed in the control group. Transplanted dLNs induced the infiltration of immune cells, which subsequently integrated into the preexisting lymphatic system. Compared with those in the control group or sham group, the number of LYVE-1+ LVs in the affected limb was greater in the dLN group.

Conclusion

The dLNs scaffolds induced the infiltration of immune cells and promoted LVs regeneration, which integrated into the preexisting lymphatic system to accelerate the restoration of lymphatic drainage.

背景:目前缺乏有效的淋巴水肿预防方法。本研究的目的是探讨去细胞化淋巴结(dln)移植预防后肢淋巴水肿的能力。方法采用1%十二烷基硫酸钠和1% Triton X - 100制备sporcine dln,通过组织学和DNA定量评价其脱细胞效果。将淋巴结(LN)碎片和dln移植到小鼠体内,并于术后第四周收集样本评估生物相容性。36只SD大鼠分为对照组(淋巴清扫)、dln组(淋巴清扫和dln移植)和假手术组(腹股沟皮肤周切)。每3 d监测后肢围度。术前及术后每周行吲哚菁绿淋巴造影。在第2周和第4周采集标本进行组织学评估。结果dln具有细胞物质几乎完全缺失、空间结构保持良好、生物相容性好、诱导免疫细胞浸润等特点。与对照组相比,dLN组术后第8、12、16天平均后肢围明显减小,假手术组术后第4、8、12、16、20天平均后肢围明显减小。假手术组表现出完整的腹股沟淋巴结和淋巴引流。dLN组观察到新生儿淋巴管(lv),对照组观察到明显的皮肤回流。移植的dln诱导免疫细胞的浸润,这些细胞随后融入预先存在的淋巴系统。与对照组或假手术组相比,dLN组患肢LYVE‐1+ lv数量更多。结论dLNs支架可诱导免疫细胞浸润,促进淋巴细胞再生,淋巴细胞与原有淋巴系统融合,加速淋巴系统的恢复。
{"title":"Decellularized lymph node scaffolds accelerate restoration of lymphatic drainage in rat hind limb lymphedema","authors":"Yang Jian,&nbsp;Jian Zhou,&nbsp;Wenjie Pan,&nbsp;Jiayin Chen,&nbsp;Yanji Zhang,&nbsp;Yanqi Li,&nbsp;Xin Liu,&nbsp;Shune Xiao,&nbsp;Chenliang Deng,&nbsp;Zairong Wei","doi":"10.1002/btm2.70056","DOIUrl":"10.1002/btm2.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>There is a lack of effective lymphedema prevention methods. The objective of this study was to investigate the ability of decellularized lymph nodes (dLNs) transplantation to prevent hindlimb lymphedema.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Porcine dLNs were prepared using 1% sodium dodecyl sulfate and 1% Triton X-100, and the effectiveness of decellularization was assessed by histological assessment and DNA quantification. Lymph node (LN) fragments and dLNs were transplanted into mice, and samples were collected for evaluating biocompatibility at the fourth week postsurgery. Thirty-six SD rats were separated into a control group (lymphatic dissection), a dLNs group (lymphatic dissection and dLNs transplant) and a sham group (inguinal skin circumferentially incised). Hindlimb circumference was monitored every 3 days. Indocyanine green lymphography was performed before and every week after surgery. Samples were collected for histological assessment at the second and fourth weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The dLNs showed virtually complete absence of cellular material, maintenance of spatial structures, and good biocompatibility and induced immune cell infiltration. Compared with that of the control group, the average hindlimb circumference of the dLN group was significantly reduced on postoperative days (PODs) 8, 12, and 16, and that of the sham group was significantly reduced on PODs 4, 8, 12, 16, and 20. The sham group exhibited intact inguinal LNs and lymphatic drainage. Neonatal lymphatic vessels (LVs) were observed in the dLN group, and obvious dermal backflow was observed in the control group. Transplanted dLNs induced the infiltration of immune cells, which subsequently integrated into the preexisting lymphatic system. Compared with those in the control group or sham group, the number of LYVE-1<sup>+</sup> LVs in the affected limb was greater in the dLN group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The dLNs scaffolds induced the infiltration of immune cells and promoted LVs regeneration, which integrated into the preexisting lymphatic system to accelerate the restoration of lymphatic drainage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":"10 6","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://aiche.onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Disease modifying biomaterials for modulating mechanical allodynia in a preclinical model of rheumatoid arthritis 在类风湿关节炎的临床前模型中调节机械异常性疼痛的疾病修饰生物材料
IF 5.7 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-07-31 DOI: 10.1002/btm2.70054
Maksim Dolmat, Julia Borges Paes Lemes, Wade T. Johnson, Elizabeth L. Wilkinson, Tony L. Yaksh, Nunzio Bottini, Nisarg J. Shah

Pain is a key symptom associated with rheumatoid arthritis (RA) and can persist even in the context of overall disease control by standard-of-care disease modifying anti-rheumatic drugs (DMARDs). Analgesic agents and corticosteroids are often used to supplement DMARDs for pain relief but lack disease modifying properties, and their sustained use carries adverse risks. In this work, we characterized the progression of pain sensitivity in the SKG mouse model of RA and evaluated the potential therapeutic interventions. Male and female SKG mice, after systemic mannan injection, developed a mechanical pain phenotype and joint swelling, with a strong inverse correlation between clinical arthritis scores and pain thresholds. To test potential interventions for pain alleviation, we evaluated all-trans retinoic acid (ATRA)-loaded poly(lactic-co-glycolic acid) microparticles (ATRA-PLGA MP) administered via intra-articular injection, which we have previously demonstrated to be disease-modifying. The pain and inflammation patterns assessed by the von Frey test and clinical scoring showed ATRA-PLGA MP monotherapy reduced inflammation and alleviated mechanical allodynia in arthritic SKG mice, an effect that was amplified by combination treatments with standard-of-care agents. In early-stage arthritis, co-administration with cytotoxic T-lymphocyte-associated protein (CTLA)-4-Ig, clinically known as abatacept, delayed disease progression and sustained the reduction of mechanical allodynia. In established arthritis, sequential treatment with the corticosteroid dexamethasone (Dex) reduced cumulative disease burden and reduced mechanical allodynia. These findings highlight the potential of combining ATRA-PLGA MP with standard-of-care treatments as a potential strategy to enhance the efficacy and durability of disease modification and pain alleviation for arthritis management.

疼痛是与类风湿关节炎(RA)相关的一个关键症状,即使在使用标准治疗疾病调节抗风湿药物(DMARDs)控制整体疾病的情况下,疼痛也可能持续存在。镇痛药和皮质类固醇常被用于补充dmard以缓解疼痛,但缺乏疾病改善特性,且持续使用会带来不良风险。在这项工作中,我们在类风湿关节炎小鼠模型中描述了疼痛敏感性的进展,并评估了潜在的治疗干预措施。全身注射甘露聚糖后,雄性和雌性SKG小鼠出现机械性疼痛表型和关节肿胀,临床关节炎评分与疼痛阈值呈强负相关。为了测试缓解疼痛的潜在干预措施,我们评估了通过关节内注射给药的全反式维甲酸(ATRA)负载的聚(乳酸- co -乙醇酸)微颗粒(ATRA - PLGA MP),我们之前已经证明了它可以改善疾病。通过von Frey试验和临床评分评估的疼痛和炎症模式显示,ATRA - PLGA MP单药治疗可减轻关节炎SKG小鼠的炎症和机械异位性疼痛,与标准护理药物联合治疗可放大这一效果。在早期关节炎中,与细胞毒性T淋巴细胞相关蛋白(CTLA) - 4 - Ig(临床称为abataccept)联合用药可延缓疾病进展并持续减少机械异常性疼痛。在已确诊的关节炎中,用皮质类固醇地塞米松(Dex)进行序贯治疗可减少累积疾病负担并减少机械异常性痛。这些发现强调了ATRA - PLGA MP与标准护理治疗相结合的潜力,作为一种潜在的策略,可以提高关节炎管理中疾病改变和疼痛缓解的疗效和持久性。
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引用次数: 0
Revolutionizing cancer treatment: The multifaceted role of graphene oxide in modern oncology 革命性的癌症治疗:氧化石墨烯在现代肿瘤学中的多方面作用
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-07-30 DOI: 10.1002/btm2.70055
Yutong Wu, Ting Zhu, Kou Wu, Zean Wang, Sizhe Jiao, Jiaxin Li, Weihong Guo, Xiaoli Feng
The rising global incidence and mortality rates of cancer underscore the persistent reliance on chemotherapy as the primary treatment modality. Despite its widespread use, challenges such as chemotherapy resistance and the absence of tumor‐specific targeting have limited its efficacy, thereby necessitating the development of more effective therapeutic strategies in clinical practice. In this context, nanomaterials have opened up new avenues for cancer therapy. Among these, nanoparticles like graphene oxide (GO) exhibit significant potential due to their large specific surface area, high biocompatibility, abundance of oxygen‐containing functional groups, and exceptional biocompatibility. This review systematically summarizes the intrinsic antitumor properties of GO and emphasizes its role in enhancing the delivery and therapeutic efficacy of chemotherapeutic agents, gene drugs, and natural compounds through multiple mechanisms. It further highlights GO's potential in synergistic chemotherapy, targeted therapy, tumor monitoring platforms, and cancer vaccine development, while also discussing the manufacturing challenges that limit clinical translation, aiming to provide theoretical guidance and innovative strategies for its future application in oncology.
全球癌症发病率和死亡率的上升强调了对化疗作为主要治疗方式的持续依赖。尽管其广泛使用,但化疗耐药和缺乏肿瘤特异性靶向等挑战限制了其疗效,因此需要在临床实践中开发更有效的治疗策略。在这种情况下,纳米材料为癌症治疗开辟了新的途径。其中,像氧化石墨烯(GO)这样的纳米颗粒由于其大的比表面积、高的生物相容性、丰富的含氧官能团和卓越的生物相容性而表现出巨大的潜力。本文系统总结了氧化石墨烯固有的抗肿瘤特性,并强调了氧化石墨烯通过多种机制增强化疗药物、基因药物和天然化合物的传递和治疗效果。进一步强调氧化石墨烯在协同化疗、靶向治疗、肿瘤监测平台和癌症疫苗开发方面的潜力,同时也讨论了限制临床转化的制造挑战,旨在为其未来在肿瘤学中的应用提供理论指导和创新策略。
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引用次数: 0
Fiber‐Electrospun Hydrogel Therapy for DNP: A synergistic electrospun‐hydrogel composite for alleviating diabetic neuropathic pain via MMP9 regulation and sodium channel inhibition 纤维-电纺丝水凝胶治疗DNP:一种通过MMP9调节和钠通道抑制来减轻糖尿病神经性疼痛的协同电纺丝-水凝胶复合材料
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-07-29 DOI: 10.1002/btm2.70050
Wen Chen, Ji Chen, Yingqing Lu, Yangyuxi Chen, Xinxin Liu, Fengrui Yang
Diabetic neuropathic pain (DNP) remains a significant challenge in diabetes care, and effective therapeutic strategies are urgently needed. This study introduces an innovative electrospinning‐hydrogel composite, Fiber‐SIN/Gel‐LidC, designed for the controlled and synergistic release of Sinomenine (SIN) and Lidocaine (Lid). Bioinformatics and network pharmacology analyses identified MMP9 as a key player in DNP alleviation. The composite, composed of SIN‐loaded fibers and Lid microcrystals, ensures sustained drug release over 7 days, demonstrating excellent biocompatibility. In vivo experiments on diabetic rats revealed significant improvements in thermal and mechanical pain thresholds, along with a reduction in sciatic nerve excitability. Additionally, the composite significantly attenuated neuroinflammation, neuronal apoptosis, and morphological damage. Mechanistic studies highlighted the neuroprotective effects of Fiber‐SIN/Gel‐LidC, particularly through the regulation of MMP9 and inhibition of sodium channels. These findings suggest that Fiber‐SIN/Gel‐LidC holds great potential as an innovative biomaterial‐based approach for managing DNP, offering promising therapeutic prospects for diabetic neuropathy.
糖尿病神经性疼痛(DNP)仍然是糖尿病护理中的一个重大挑战,迫切需要有效的治疗策略。本研究介绍了一种新型的静电纺丝-水凝胶复合材料Fiber - SIN/Gel - LidC,用于青藤碱(SIN)和利多卡因(Lid)的控制和协同释放。生物信息学和网络药理学分析确定MMP9在DNP缓解中起关键作用。该复合材料由装载SIN的纤维和Lid微晶体组成,可确保药物持续释放超过7天,并表现出良好的生物相容性。糖尿病大鼠的体内实验显示,热痛阈和机械痛阈显著改善,坐骨神经兴奋性降低。此外,该复合物还能显著减轻神经炎症、神经元凋亡和形态学损伤。机制研究强调了纤维- SIN/凝胶- LidC的神经保护作用,特别是通过调节MMP9和抑制钠通道。这些研究结果表明,Fiber - SIN/Gel - LidC作为一种创新的基于生物材料的DNP治疗方法具有巨大的潜力,为糖尿病神经病变的治疗提供了广阔的前景。
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引用次数: 0
Neuron‐targeted 2‐deoxyglucose‐dendrimer‐rosiglitazone nanotherapy mitigates neuroinflammation and cognitive deficits in pediatric traumatic brain injury 神经元靶向2 -脱氧葡萄糖-树突状聚合物-罗格列酮纳米疗法减轻小儿创伤性脑损伤的神经炎症和认知缺陷
IF 7.4 2区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2025-07-23 DOI: 10.1002/btm2.70053
Aqib Iqbal Dar, Zhi Zhang, Shamila Gopalakrishnan, Rishi Sharma, Anunay James Pulukuri, Anu Rani, Anubhav Dhull, Joan Castaneda Gonzalez, Tia Atoui, Yara Mashal, Zahrah Naseer, Julia Calmi, Anjali Sharma
Traumatic brain injury (TBI) remains a major global health challenge, characterized by high morbidity and mortality rates. Despite advances in neuroscience, the blood–brain barrier (BBB) limits the effectiveness of potential neuroprotective treatments. Recent nanotechnology breakthroughs have led to smart drug delivery systems that can cross the BBB and target injured brain areas. However, achieving the specificity needed to deliver therapies to affected neurons remains a challenge. In previous work, we developed a mixed‐layered dendrimer functionalized with 2‐deoxyglucose (2DG‐D) for selective neuronal drug delivery. In this study, we explore the therapeutic potential of rosiglitazone (Rosi) for pediatric TBI by creating a 2DG‐D‐Rosi nanosystem, where Rosi is conjugated to 2DG‐D to improve its solubility, bioavailability, and targeted delivery to injured neurons. In vitro, 2DG‐D‐Rosi demonstrated high neuronal uptake, sustained drug release, and excellent biocompatibility. It significantly reduced neuronal apoptosis, reactive oxygen species formation, pro‐inflammatory cytokine expression, and caspase activity, outperforming free Rosi. In vivo, using a pediatric TBI mouse model, 2DG‐D‐Rosi improved neuronal targeting, reduced neuroinflammation, and enhanced behavioral outcomes. This research highlights 2DG‐D‐Rosi as a promising nanotherapeutic platform for precise TBI treatment and sets the stage for developing more effective therapies for this challenging condition.
外伤性脑损伤(TBI)仍然是一个主要的全球健康挑战,其特点是发病率和死亡率高。尽管神经科学取得了进步,但血脑屏障(BBB)限制了潜在的神经保护治疗的有效性。最近的纳米技术突破已经导致了智能药物输送系统,可以穿过血脑屏障,瞄准受伤的大脑区域。然而,实现对受影响神经元提供治疗所需的特异性仍然是一个挑战。在之前的工作中,我们开发了一种具有2 -脱氧葡萄糖(2DG - D)功能化的混合层状树状大分子,用于选择性神经元药物递送。在这项研究中,我们通过创建2DG‐D‐Rosi纳米系统来探索罗格列酮(Rosi)对儿科TBI的治疗潜力,其中Rosi与2DG‐D结合以提高其溶解度,生物利用度和靶向递送到受损神经元。在体外,2DG‐D‐Rosi表现出高的神经元摄取、持续的药物释放和良好的生物相容性。它显著降低了神经元凋亡、活性氧形成、促炎细胞因子表达和半胱天冬酶活性,优于游离Rosi。在体内,使用儿童TBI小鼠模型,2DG‐D‐Rosi改善了神经元靶向性,减少了神经炎症,并增强了行为结果。这项研究突出了2DG - D - Rosi作为精确治疗TBI的有前途的纳米治疗平台,并为开发更有效的治疗这种具有挑战性的疾病奠定了基础。
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Bioengineering & Translational Medicine
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