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Decellularized extracellular matrix: Advanced bioplatforms for functional tissue restoration via innovative decellularization techniques 脱细胞细胞外基质:通过创新的脱细胞技术实现功能性组织修复的先进生物平台
Pub Date : 2026-01-08 DOI: 10.1016/j.bmt.2025.100131
Zhe Wang , Xiang Lin , Yunpeng Shi , Hong Yan , Yixuan Shang , Haozhen Ren

Background

In recent years, tissue engineering has experienced rapid development, with bioscaffolds emerging as a focal point of research due to their favorable bioactivity, biocompatibility, and capacity to provide mechanical support for cellular growth. The bioscaffolds have great potential in tissue regeneration. However, conventional natural scaffolds and polymer scaffolds pose risks of immunogenicity, while also face challenges in mimicking the in vivo microenvironment and the biochemical and mechanical properties of natural organs/tissues, which collectively limit their repair capability. The development of decellularized extracellular matrix (dECM) technology offers a viable solution to these challenges, demonstrating considerable potential for advancing organ and tissue regeneration.

Technology

This reviews the classification of dECM, outlines various current methods for its preparation, and comprehensively examines its latest advances in tissue repair and regenerative medicine, including applications in skin, bone, nerve, heart, lung, liver, and kidney tissues.

Results

This review systematically examines recent advances in dECM production and regenerative medicine applications. We classify dECM subtypes, detail contemporary decellularization protocols, and highlight their biomedical utility. Superior biocompatibility substantially mitigates post-transplant immune rejection risk, underscoring strong clinical translation potential for tissue engineering.
近年来,组织工程得到了快速发展,生物支架因其良好的生物活性、生物相容性和为细胞生长提供机械支持的能力而成为研究的热点。生物支架在组织再生方面具有很大的潜力。然而,传统的天然支架和聚合物支架存在免疫原性风险,同时在模仿天然器官/组织的体内微环境和生化力学特性方面也面临挑战,这些共同限制了它们的修复能力。脱细胞细胞外基质(dECM)技术的发展为这些挑战提供了可行的解决方案,显示出推进器官和组织再生的巨大潜力。本文综述了dECM的分类,概述了dECM目前的各种制备方法,并全面研究了dECM在组织修复和再生医学方面的最新进展,包括在皮肤、骨骼、神经、心脏、肺、肝和肾组织中的应用。结果本文系统地综述了dECM生产和再生医学应用的最新进展。我们对dECM亚型进行分类,详细介绍当代脱细胞方案,并强调其生物医学用途。优越的生物相容性大大降低了移植后的免疫排斥风险,强调了组织工程的强大临床转化潜力。
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引用次数: 0
Wireless bioelectric stimulation for bone regeneration using magnetoelectric PVDF/BaTiO3 – Fe80Ga20 laminates 利用磁电PVDF/BaTiO3 - Fe80Ga20层压板进行骨再生的无线生物电刺激
Pub Date : 2025-11-20 DOI: 10.1016/j.bmt.2025.100121
H.A. Viraji , Aravinda Abeygunawardane , S.U. Adikary , Sajith Edirisinghe , Aadil Faleel
<div><div>Fracture healing remains a significant clinical challenge, particularly in cases of delayed or impaired recovery, often hindered by inadequate vascularization, patient variability. Conventional stimulation methods relying on implanted electrodes or external coils are constrained by invasiveness, complexity, and patient discomfort. Smart biomaterials capable of providing wireless, localized bioelectric stimulation represent a promising alternative. Among these, magnetoelectric (ME) laminates can convert externally applied magnetic fields into localized therapeutic voltages, enabling non-invasive and patient-specific bone regeneration. Although magnetoelectric systems have shown potential in biomedical stimulation, their electromechanical coupling behavior, tunability, and optimization for orthopedic applications remain insufficiently explored. Understanding these mechanisms through computational modeling is crucial for developing clinically translatable ME-based bone regeneration systems. This study introduces a next-generation trilayer ME laminate integrating a new material pairing: magnetostrictive Galfenol (Fe<sub>80</sub>Ga<sub>20</sub>) with a piezoelectric layer of either poly(vinylidene fluoride)(PVDF) or Barium Titanate (BaTiO<sub>3</sub>). A fully coupled 3D finite-element model was developed in COMSOL Multiphysics 6.0 to simulate magnetostrictive deformation, interfacial strain transfer, and piezoelectric voltage generation under physiologically relevant magnetic field strengths and frequencies. Parametric studies assessed tunability across varying excitation conditions, while comparative analyses evaluated the performance trade-offs between PVDF- and BaTiO<sub>3</sub>-based laminates. Simulations revealed that the proposed trilayer laminate could generate sustained voltage outputs within the osteogenesis-relevant range (100 nV–5 V) without implanted electrodes. Resonance-dependent voltage peaks were sensitive to excitation frequency and adaptable to bone geometry, supporting personalized stimulation protocols. PVDF-based laminates provided higher flexibility and biocompatibility, whereas BaTiO<sub>3</sub>-based laminates achieved superior voltage outputs, highlighting design trade-offs relevant for clinical optimization. This work establishes the engineering feasibility and fundamental electromechanical characteristics of magnetoelectric trilayer laminates for wireless bone stimulation. The deterministic modeling approach, incorporating parameter sweeps for laminate thickness, field amplitude, and excitation frequency, provides a first-level sensitivity framework for device design. Overall, the study bridges computational modeling and translational potential, positioning ME laminates as a next-generation platform for non-invasive, customizable, and patient-centered bone regeneration. These findings lay the groundwork for forthcoming <em>in-vitro</em> and <em>in-vivo</em> validations, advancing the integration of smart magnetoe
骨折愈合仍然是一个重大的临床挑战,特别是在延迟或受损恢复的情况下,通常受到血管化不足和患者变异性的阻碍。依靠植入电极或外部线圈的传统刺激方法受到侵入性、复杂性和患者不适的限制。能够提供无线、局部生物电刺激的智能生物材料是一个很有前途的选择。其中,磁电(ME)层压板可以将外部施加的磁场转换为局部治疗电压,从而实现非侵入性和患者特异性骨再生。尽管磁电系统在生物医学刺激方面显示出潜力,但其机电耦合行为、可调性和骨科应用的优化仍未得到充分探索。通过计算建模了解这些机制对于开发临床可翻译的基于me的骨再生系统至关重要。本研究介绍了一种新一代三层ME层压板,集成了一种新的材料组合:磁致伸缩Galfenol (Fe80Ga20)与聚偏氟乙烯(PVDF)或钛酸钡(BaTiO3)的压电层。在COMSOL Multiphysics 6.0中建立了全耦合三维有限元模型,模拟了与生理相关的磁场强度和频率下的磁致伸缩变形、界面应变传递和压电电压产生。参数研究评估了不同激励条件下的可调性,而比较分析评估了PVDF和batio3基层压板之间的性能权衡。模拟结果表明,在不植入电极的情况下,所提出的三层层叠板可以在成骨相关范围内(100 nV-5 V)产生持续的电压输出。谐振相关的电压峰值对激励频率敏感,并适应骨的几何形状,支持个性化的刺激方案。pvdf基层压板具有更高的灵活性和生物相容性,而batio3基层压板具有优越的电压输出,突出了与临床优化相关的设计权衡。本工作确立了磁电三层复合材料用于无线骨刺激的工程可行性和基本机电特性。确定性建模方法结合层压厚度、场振幅和激励频率的参数扫描,为器件设计提供了一级灵敏度框架。总的来说,该研究将计算建模和转化潜力结合起来,将ME层压板定位为下一代无创、可定制和以患者为中心的骨再生平台。这些发现为即将到来的体外和体内验证奠定了基础,推进了智能磁电材料在临床骨科应用中的整合。
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引用次数: 0
Microenvironment-feedback hydrogel for precise sequential repair of acute infectious wounds 微环境反馈水凝胶用于急性感染性伤口的精确顺序修复
Pub Date : 2025-11-19 DOI: 10.1016/j.bmt.2025.100120
Zixuan Tang , Qingquan Xia , Jian Li , Jun Chen , Xuhua Wu , Jiang Li , Jiangyi Liu , Wei Liu , Ke Rong , Xiangchao Meng
The healing of acute infected wounds is a multi-stage and sequential biological process. Traditional antibacterial dressings are usually a simple superposition of antibacterial properties and active ingredients, lacking effective coupling with the wound microenvironment, and it is difficult to accurately match the continuous process of infected wound healing. In this study, a pH-responsive hydrogel of sodium alginate and carboxymethyl chitosan interpenetrating network was constructed, and tannic acid (TA) and zinc-doped bioglass (BAG) were loaded through hydrogen bonding and hydrophobic interactions. In the acidic environment of infection, the enhancement of intermolecular non-covalent interaction leads to the contraction of hydrogel network and the rapid release of TA. In the alkaline environment of healing, the weakening of intermolecular interaction leads to the expansion of hydrogel network and the continuous release of Zn2+ and Ca2+. In vitro biological evaluation showed that the hydrogel had an effective antibacterial effects against E.coli and S.aureus, and effectively regulated immune response. In addition, the hydrogel effectively removed excessive ROS and significantly increase the activity of cellular antioxidant enzymes, thereby accelerating the wound healing process in animal experiment. This microenvironment-responsive hydrogel provides a new therapeutic strategy for precise sequential repair of acute infectious wounds.
急性感染创面的愈合是一个多阶段连续的生物学过程。传统抗菌敷料通常是抗菌性能与有效成分的简单叠加,缺乏与创面微环境的有效耦合,难以准确匹配感染创面愈合的连续过程。本研究构建了海藻酸钠和羧甲基壳聚糖的ph响应水凝胶互穿网络,通过氢键和疏水相互作用负载单宁酸(TA)和锌掺杂生物玻璃(BAG)。在感染的酸性环境中,分子间非共价相互作用的增强导致水凝胶网络收缩,TA快速释放。在愈合的碱性环境中,分子间相互作用的减弱导致水凝胶网络的扩张和Zn2+和Ca2+的持续释放。体外生物学评价表明,水凝胶对大肠杆菌和金黄色葡萄球菌具有有效的抗菌作用,并能有效调节免疫反应。此外,在动物实验中,水凝胶可以有效去除过量的ROS,显著提高细胞抗氧化酶的活性,从而加速伤口愈合过程。这种微环境反应性水凝胶为急性感染性伤口的精确顺序修复提供了一种新的治疗策略。
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引用次数: 0
Targeting Fcgr1 to repress FAPy-adenine-induced osteoporosis in osteosarcoma receiving chemotherapy 靶向Fcgr1抑制化疗骨肉瘤中fapy腺嘌呤诱导的骨质疏松
Pub Date : 2025-11-14 DOI: 10.1016/j.bmt.2025.100118
Wei Xu , Liwen Song , Qifeng Yu , Shichao Tong , Yi Wang , Yifan Li , Jin Qiu , Zhikun Li
Chemotherapy-induced bone loss in patients with osteosarcoma (OS) has attracted increasing attention worldwide. Previous studies have revealed the interactions between OS cells and osteoclasts via secretion of various cytokines. However, the specific impacts of chemically injured OS cells on osteoclast functions remain unknown. Untargeted metabolomics is a high-throughput analytical technique used to screen potential biomarkers and identify unknown metabolites in various biological samples. In this study, cisplatin (CDDP)-injured OS cell supernatant promoted the osteoclast differentiation of bone marrow macrophages (BMMs). Untargeted metabolomic analysis revealed the metabolic profile of injured OS cells, and FAPy-adenine (FA), which was upregulated by approximately 2000-fold, was identified in the supernatant. FA promoted the osteoclast differentiation of BMMs in a dose-dependent manner. RNA sequencing revealed increased Fc gamma receptor 1 (Fcgr1) expression levels in FA-treated BMMs. Fcgr1 overexpression promoted the osteoclast differentiation of BMMs and Cathepsin K expression, whereas its knockdown inhibited the pro-osteoclast differentiation effect of FA. Furthermore, FA accelerated osteoporosis progression in ovariectomy model rats. Upregulation of Fcgr1 levels promoted bone loss, whereas its silencing inhibited the bone loss induced by FA in ovariectomy model rats. Collectively, these findings suggest that FA released from CDDP-injured OS cells contributes to osteoporosis progression by upregulating Fcgr1 levels, providing new insights into chemotherapy-induced bone loss in patients with OS.
骨肉瘤(OS)患者化疗引起的骨丢失在世界范围内引起了越来越多的关注。先前的研究揭示了骨肉瘤细胞与破骨细胞之间通过分泌各种细胞因子的相互作用。然而,化学损伤的骨肉瘤细胞对破骨细胞功能的具体影响尚不清楚。非靶向代谢组学是一种高通量分析技术,用于筛选潜在的生物标志物和鉴定各种生物样品中的未知代谢物。在本研究中,顺铂(CDDP)损伤的OS细胞上清可促进骨髓巨噬细胞(BMMs)的破骨细胞分化。非靶向代谢组学分析揭示了受损OS细胞的代谢谱,在上清中发现了大约上调2000倍的fapy -腺嘌呤(FA)。FA促进BMMs破骨细胞分化呈剂量依赖性。RNA测序显示,fa处理的bmm中Fc γ受体1 (Fcgr1)表达水平升高。Fcgr1过表达促进BMMs的破骨细胞分化和Cathepsin K的表达,而下调Fcgr1则抑制FA的促破骨细胞分化作用。此外,FA加速了卵巢切除模型大鼠骨质疏松症的进展。在卵巢切除模型大鼠中,上调Fcgr1水平可促进骨质流失,而沉默Fcgr1水平可抑制FA诱导的骨质流失。总之,这些发现表明,从cddp损伤的骨肉瘤细胞释放的FA通过上调Fcgr1水平促进骨质疏松症的进展,为化疗诱导的骨丢失在骨肉瘤患者中提供了新的见解。
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引用次数: 0
Multi-omics advances in understanding cancer drug resistance 多组学在了解癌症耐药性方面的进展
Pub Date : 2025-11-14 DOI: 10.1016/j.bmt.2025.100119
Xuechao Liu , Kunpeng Wei , Enyu Lin , Yi Li , Pengzhen Zhuang , Yanbing Zhou , Guilai Zuo , Zhaojian Niu
Cancer drug resistance presents a significant challenge in modern oncology, necessitating detailed exploration of its underlying mechanisms and the development of effective counterstrategies. This review aims to systematically evaluate the most recent applications and advancements of multi-omics technologies in elucidating the mechanisms of cancer drug resistance. Multi-omics includes genomics, transcriptomics, proteomics, microbiomics, metabolomics, and epigenomics. Notably, emerging methodologies such as single-cell and spatial omics have been instrumental in revealing the biological characteristics and resistance mechanisms of tumor cells across various layers and dimensions. The review highlights resistance mechanisms uncovered through the combined application of multi-omics, including gene mutations and epigenetic modifications, reprogramming of signaling pathways, drug efflux and cytoskeletal reorganization, and DNA repair mechanisms. It also explores novel mechanisms in the tumor immune microenvironment (TIME), metabolic reprogramming, and microbiome interactions. The review assesses the benefits of integrating multi-omics data, the application of these technologies in identifying key genes and pathways, and their role in personalized treatment strategies. It provides a comprehensive understanding of the dynamic changes and heterogeneity in cancer drug resistance to aid precision treatment strategies. Additionally, the article offers insights into the future directions of multi-omics technologies in oncology drug resistance research and discusses the primary challenges ahead. We aim to provide novel perspectives and directions for innovation and optimization in cancer treatment, ultimately enhancing patient prognosis and quality of life in oncology.
癌症耐药是现代肿瘤学的一个重大挑战,需要对其潜在机制进行详细的探索,并制定有效的应对策略。本文综述了多组学技术在肿瘤耐药机制研究中的最新应用和进展。多组学包括基因组学、转录组学、蛋白质组学、微生物组学、代谢组学和表观基因组学。值得注意的是,单细胞组学和空间组学等新兴方法有助于揭示肿瘤细胞在不同层次和维度上的生物学特性和耐药机制。本文重点介绍了通过多组学联合应用揭示的耐药机制,包括基因突变和表观遗传修饰、信号通路重编程、药物外排和细胞骨架重组以及DNA修复机制。它还探讨了肿瘤免疫微环境(TIME)、代谢重编程和微生物组相互作用的新机制。这篇综述评估了整合多组学数据的好处,这些技术在识别关键基因和通路中的应用,以及它们在个性化治疗策略中的作用。它提供了对癌症耐药的动态变化和异质性的全面了解,以帮助精确的治疗策略。此外,本文还提出了多组学技术在肿瘤耐药研究中的未来方向,并讨论了未来的主要挑战。我们的目标是为肿瘤治疗的创新和优化提供新的视角和方向,最终提高肿瘤患者的预后和生活质量。
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引用次数: 0
Integrative cell subtype-to-drug discovery technology for angiomyolipomas ​treatment 血管平滑肌脂肪瘤治疗的整合细胞亚型-药物发现技术
Pub Date : 2025-11-06 DOI: 10.1016/j.bmt.2025.100117
Junxian Cao , Xiao Chang , Shiwen Deng , Hongjun Yang , Gang Guo , Peng Chen
Tuberous sclerosis complex mutation renal angiomyolipomas (TSC-RAML) are benign tumors driven by abnormal growth of mesenchymal-derived cells. Although mTOR inhibitors are clinically used, drug resistance and incomplete tumour shrinkage highlight the need for new treatment approaches. Here, we developed a new strategy combining single-cell transcriptomics, network pharmacology, and functional experiments to identify targeted therapies for TSC-RAMLs. Single-cell RNA sequencing of tumour tissues from 4 TSC-RAML patients uncovered a distinct mesenchymal subpopulation (TSC-RAML-Cells) with upregulated pathways in adipogenesis and mTOR signalling. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA) on TSC-RAML-Cells, we identified three disease-associated modules containing hub genes critical for tumour survival. Cross-referencing these modules with the Connectivity Map (CMAP) drug database prioritized AS-605240 as a potential therapeutic candidate. Protein-protein interaction (PPI) network analysis further revealed PI3KCA as a central target, and molecular dynamics simulations confirmed stable binding between AS-605240 and PI3KCA, with a binding free energy of −7.8 ​kcal/mol, supporting its mechanism of action. In vitro experiments using patient-derived TSC-RAML cells showed that AS-605240 suppressed cell growth in a dose-dependent manner (IC50 ​= ​7.8 ​μM) and increased apoptosis rates through inhibition of the PI3K/AKT pathway. This work not only proposes AS-605240 as a promising therapy for TSC-RAMLs but also provides a scalable “cell subtype-to-drug" discovery framework. By integrating single-cell omics and computational drug repurposing, this approach accelerates precision medicine development for rare diseases.
结节性硬化复杂突变肾血管平滑肌脂肪瘤(TSC-RAML)是由间充质来源细胞异常生长驱动的良性肿瘤。尽管临床上使用mTOR抑制剂,但耐药和肿瘤不完全缩小突出了对新治疗方法的需求。在这里,我们开发了一种结合单细胞转录组学、网络药理学和功能实验的新策略,以确定TSC-RAMLs的靶向治疗方法。对4例TSC-RAML患者肿瘤组织的单细胞RNA测序发现了一个独特的间充质亚群(TSC-RAML细胞),其脂肪形成和mTOR信号通路上调。利用tsc - raml细胞的高维加权基因共表达网络分析(hdWGCNA),我们确定了三个包含对肿瘤生存至关重要的中心基因的疾病相关模块。将这些模块与Connectivity Map (CMAP)药物数据库进行交叉比对,优先考虑as -605240作为潜在的治疗候选药物。蛋白-蛋白相互作用(PPI)网络分析进一步揭示PI3KCA为中心靶点,分子动力学模拟证实as -605240与PI3KCA结合稳定,结合自由能为−7.8 kcal/mol,支持其作用机制。体外实验表明,AS-605240通过抑制PI3K/AKT通路,呈剂量依赖性抑制细胞生长(IC50 = 7.8 μM),增加细胞凋亡率。这项工作不仅提出了as -605240作为tsc - raml的一种有希望的治疗方法,而且还提供了一个可扩展的“细胞亚型到药物”发现框架。通过整合单细胞组学和计算药物再利用,这种方法加速了罕见病精准医学的发展。
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引用次数: 0
Adoptive cell therapy for HBV-associated liver diseases 乙肝病毒相关肝病的过继细胞治疗
Pub Date : 2025-11-03 DOI: 10.1016/j.bmt.2025.100116
Youxi Zhou , Kaizhao Chen , Yang Zhang , Hongwei Cheng , Shuaishuai Zhang
Chronic infection with the hepatitis B virus (HBV) is a common cause of liver disease worldwide, particularly in Asia and Africa, where it is highly prevalent. Currently, therapies for chronic HBV infection, such as nucleoside analogs (NAs), mainly suppress viral replication but rarely achieve a lasting cure. Recently, emerging adoptive cell therapy (ACT), represented by chimeric antigen receptor (CAR)-T, T cell receptor (TCR)-T, and CAR-NK (Natural Killer) cell therapy, have provided new opportunities for the treatment of numerous diseases. For instance, CAR-T cells can be designed to target HBV antigens and kill HBV-infected cells with safety concerns regarding potential side effects and limitations of CAR-T cell exhaustion. TCR-T cells mainly exert their immune activation effects by recognizing antigen peptide-MHC complexes in HBV-infected hepatocytes. Although the antiviral effects of TCR-T are evident in preclinical studies, they are limited by on-target toxicity and carry a risk of transient liver damage. In addition to CAR-T and TCR-T therapies, CAR-NK cell therapy has shown promising prospects in treating HBV-associated liver diseases. To enhance the safety and efficiency of ACT applications in clinical settings, CAR and TCR structures should be rationally optimized, and combined treatment strategies need to be explored. In this review, we summarize the structure and mechanism of ACT, including CAR-T, TCR-T, and CAR-NK cell therapies, as well as their research progress and challenges in the treatment of HBV-associated liver diseases.
慢性乙型肝炎病毒(HBV)感染是世界范围内肝病的常见原因,特别是在亚洲和非洲,这是非常普遍的。目前,治疗慢性HBV感染的方法,如核苷类似物(NAs),主要是抑制病毒复制,但很少能实现持久治愈。近年来,以嵌合抗原受体(CAR)-T、T细胞受体(TCR)-T和CAR- nk(自然杀伤细胞)细胞疗法为代表的过继细胞疗法(ACT)为多种疾病的治疗提供了新的机会。例如,CAR-T细胞可以设计为靶向HBV抗原并杀死HBV感染的细胞,但存在潜在副作用和CAR-T细胞衰竭的安全性问题。TCR-T细胞主要通过识别hbv感染的肝细胞中的抗原肽- mhc复合物来发挥其免疫激活作用。尽管TCR-T的抗病毒作用在临床前研究中是明显的,但它们受到靶毒性的限制,并有短暂肝损伤的风险。除了CAR-T和TCR-T疗法外,CAR-NK细胞疗法在治疗hbv相关肝脏疾病方面也显示出良好的前景。为提高ACT在临床应用的安全性和效率,应合理优化CAR和TCR结构,探索联合治疗策略。本文综述了ACT的结构和作用机制,包括CAR-T、TCR-T和CAR-NK细胞疗法,以及它们在治疗hbv相关肝脏疾病中的研究进展和挑战。
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引用次数: 0
Precision and customization in regenerative medicine: The role of coaxial 3D printing 再生医学中的精度和定制化:同轴3D打印的作用
Pub Date : 2025-10-28 DOI: 10.1016/j.bmt.2025.100115
Shengwen Cheng , Jiaying Wei , Senrui Liu , Junyan Liu , Xiaohong Luo , Yixuan Lan , Mingfei Dong , Liangbin Zhou , Wei Huang , Chen Zhao , Yiting Lei
Coaxial three-dimensional (3D) printing enables precise, multi-material deposition, demonstrating strong potential across diverse fields, including industrial monitoring, health sensing, artificial intelligence (AI) hardware, and food packaging. Its core value is prominently realized in the biomedical domain, where it has revolutionized tissue engineering. The present review consolidates advancements in 3D coaxial bioprinting across diverse biomedical applications, focusing on its transformative potential in vascularized tissue engineering, spatiotemporal drug delivery, and patient-specific disease modeling. This review also explored unresolved challenges, such as bioink optimization and functional vascularization, while proposing integrative solutions that combine coaxial printing with AI and hybrid fabrication strategies. The versatility of coaxial 3D printing is evident in its numerous biomedical applications, such as cardiovascular tissue engineering, skin regeneration, bone repair, and functional muscle constructs. In bone tissue engineering, coaxial printing facilitates vascularization and osteochondral regeneration through spatially controlled bioink and scaffold design. Applications extend to cartilage repair, neuromuscular junction modeling, and tumor microenvironment replication. Despite progress, challenges persist in optimizing bioink rheology, achieving functional vascularization, and scaling production for clinical application. Notably, the integration of advanced materials, such as hydrogels and inorganic salts, with hybrid strategies, including electrospinning and sacrificial printing, highlights the synergistic potential of coaxial bioprinting to transform regenerative medicine, drug screening, and personalized therapies. Ongoing innovations in multi-scale, multi-cellular printing can bridge the gap between engineered constructs and biological functional tissues.
同轴三维(3D)打印可实现精确的多材料沉积,在工业监控、健康传感、人工智能(AI)硬件和食品包装等多个领域显示出强大的潜力。它的核心价值在生物医学领域得到了突出的体现,它彻底改变了组织工程。本综述整合了3D同轴生物打印在不同生物医学应用中的进展,重点关注其在血管化组织工程、时空药物输送和患者特异性疾病建模方面的变革潜力。本文还探讨了尚未解决的挑战,如生物链接优化和功能性血管化,同时提出了将同轴打印与人工智能和混合制造策略相结合的综合解决方案。同轴3D打印的多功能性在其众多生物医学应用中是显而易见的,例如心血管组织工程,皮肤再生,骨骼修复和功能性肌肉结构。在骨组织工程中,同轴打印通过空间控制的生物链接和支架设计促进血管化和骨软骨再生。应用扩展到软骨修复,神经肌肉连接建模和肿瘤微环境复制。尽管取得了进展,但在优化生物链流变学、实现功能性血管化和规模化生产临床应用方面仍然存在挑战。值得注意的是,将水凝胶和无机盐等先进材料与包括静电纺丝和牺牲打印在内的混合策略相结合,突出了同轴生物打印在改变再生医学、药物筛选和个性化治疗方面的协同潜力。不断创新的多尺度、多细胞打印技术可以弥合工程结构和生物功能组织之间的差距。
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引用次数: 0
Prodrug nanoassembly technology for colorectal cancer therapy 前药纳米组装技术用于结直肠癌治疗
Pub Date : 2025-10-27 DOI: 10.1016/j.bmt.2025.100114
Qing Wang , Shiyi Zuo , Xixuan Yang , Yaqi Li , Cuiyun Liu , Yaqiao Li , Shuo Wang , Wenjing Wang , Danping Wang , Jiayu Guo , Jin Sun , Zhonggui He , Zhenbao Li , Bingjun Sun
The clinical efficacy of Irinotecan is constrained by individual variability in its enzymatic conversion to the active metabolite, SN38. While direct administration of SN38 bypasses this enzymatic process and demonstrates potent anti-tumor activity, its clinical application remains hindered by poor physicochemical properties and off-target toxicity. These challenges highlight the necessity for efficient drug delivery strategies. Prodrug nanoassemblies combine the advantages of nano drug delivery technology and prodrug strategy, offering an effective approach to address these limitations. The modification module in prodrug design plays a critical role in imparting prodrugs self-assembly ability. Monomethyl branched-chain fatty acids (mmBCFAs), known for their biocompatibility and metabolite safety, show great potential as a worthy option. In this study, we designed and synthesized SN38-SS-BAc18 by incorporating 16-methylheptanoic acid (BAc18) as the modification module, and a disulfide bond as the responsive module for tumor-specific activation. The resulting SN38-SS-BAc18 significantly improved the undesirable physicochemical properties of SN38 and exhibited enhanced self-assembly performance. Due to its prolonged circulation time, high tumor accumulation, and specific release profiles, the prodrug nanoassemblies (SN38-SS-BAc18 NPs) exhibited superior anti-tumor efficacy and biosafety. This study addressed multiple therapeutic limitations of SN38 and Irinotecan, providing valuable insights for the rational design of efficient prodrug nanoassemblies for colorectal cancer treatment.
伊立替康的临床疗效受到其酶转化为活性代谢物SN38的个体差异的限制。虽然直接给药SN38可以绕过这一酶促过程并显示出强大的抗肿瘤活性,但其物理化学性质差和脱靶毒性仍阻碍了其临床应用。这些挑战突出了制定有效给药战略的必要性。前体药物纳米组件结合了纳米药物传递技术和前体药物策略的优点,为解决这些局限性提供了有效的途径。前体药物设计中的修饰模块对赋予前体药物自组装能力起着至关重要的作用。单甲支链脂肪酸(mmBCFAs)以其生物相容性和代谢安全性而闻名,显示出作为一种有价值的选择的巨大潜力。本研究以16-甲基庚酸(BAc18)为修饰模块,以二硫键为肿瘤特异性激活响应模块,设计合成了SN38-SS-BAc18。所得SN38- ss - bac18显著改善了SN38的理化性质,并表现出增强的自组装性能。SN38-SS-BAc18纳米组件具有循环时间长、肿瘤蓄积大、释放特异性强等特点,具有良好的抗肿瘤疗效和生物安全性。本研究解决了SN38和伊立替康的多重治疗局限性,为合理设计有效的结直肠癌治疗前药纳米组件提供了有价值的见解。
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A high-throughput immunopeptidome platform for MHC II alleles to characterize antigen-specific CD4+ T cells MHC II等位基因的高通量免疫肽球平台,表征抗原特异性CD4+ T细胞
Pub Date : 2025-09-27 DOI: 10.1016/j.bmt.2025.100112
Jing Chen , Xu Zhu , Jun Huo , Shang Wu , Ting Zhou , Chunyu Cheng , Hao Dong , Yan Li , Xianchi Dong , Yuxin Chen
CD4+ T cells play a pivotal role in adaptive immunity, recognizing peptide antigens presented by MHC II molecules during infections and tumor development. Identifying immunodominant MHC II epitopess is essential for understanding CD4+ T cell responses; however, current methods such as mass spectrometry, suffer from low sensitivity and throughput, while computational algorithms show variable accuracy. To overcome these challenges, we developed EliteMHCII, a high-throughput immunopeptidome profiling platform that identifies antigen-derived MHC II epitopes and measures peptide binding affinity across 24 globally common MHC II alleles. Using EliteMHCII, we assessed the immunodominant epitopes of the SARS-CoV-2 RBD protein. Validation in vaccinated individuals and humanized mouse models revealed a strong correlation between high-affinity peptides and robust CD4+ T cell responses, while low-affinity peptides failed to elicit responses. Therefore, our immunopeptidome profiling platform, EliteMHCII, serves as a rapid, high throughput, feasible platform for CD4+ T cell epitope discovery at a global populational level in the context of infectious diseases and cancer immunotherapy.
CD4+ T细胞在适应性免疫中发挥关键作用,在感染和肿瘤发展过程中识别MHC II分子呈递的肽抗原。识别免疫显性MHC II表位对于理解CD4+ T细胞反应至关重要;然而,目前的方法,如质谱法,受到低灵敏度和吞吐量的影响,而计算算法显示出可变的准确性。为了克服这些挑战,我们开发了EliteMHCII,这是一个高通量免疫肽球分析平台,可以识别抗原来源的MHCII表位,并测量24个全球常见的MHCII等位基因的肽结合亲和力。使用EliteMHCII,我们评估了SARS-CoV-2 RBD蛋白的免疫优势表位。在接种疫苗个体和人源化小鼠模型中的验证表明,高亲和力肽与稳健的CD4+ T细胞应答之间存在很强的相关性,而低亲和力肽无法引起应答。因此,我们的免疫肽分析平台EliteMHCII可作为一个快速、高通量、可行的平台,在传染病和癌症免疫治疗的背景下,在全球人群水平上发现CD4+ T细胞表位。
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Biomedical Technology
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