Engineered regeneration最新文献

Harnessing the interplay between tendon stem/progenitor cell and microenvironment boosts tendon tissue regeneration 利用肌腱干/祖细胞与微环境之间的相互作用促进肌腱组织再生

Q1 Medicine

Engineered regeneration

Pub Date : 2026-01-01 DOI: 10.1016/j.engreg.2025.11.004

Hong Zhang , Yujian Xu , Yangwu Chen , Kun Zhao , Tianshun Fang , Youguo Liao , Xiangming Ye , Xiao Chen , Zi Yin

Tendon injuries are common musculoskeletal disorders characterized by limited natural healing capacity and inability to restore the original structure and function of tendons. Tendon tissue engineering based on tendon stem/progenitor cells (TSPCs) offers a potential strategy for tendon injury treatments. The function regulation of TSPCs is influenced by both in vivo and in vitro microenvironmental factors. Here, we provide a concise summary of the various subpopulations of TSPCs identified thus far. Additionally, we explore the current research progress on the in vivo microenvironment of TSPCs. Notably, we first introduce the concept of a "degeneration loop," which highlights the intricate interplay between the tendon microenvironment and TSPCs. Developing from this concept, we derive the theory and strategic framework of "Remodel niche - Disrupt Degeneration Loop - Tendon Healing" for effective tendon regeneration. Furthermore, we present an overview of the latest advances in the regulation of TSPCs expansion and differentiation through manipulation of the microenvironment in vitro and in vivo. Lastly, we address the challenges and related prospects encountered in the regenerative application of TSPCs subpopulations. A deeper multi-scale understanding of the interplay between distinct TSPCs subpopulations and their microenvironment will greatly contribute to the development of innovative tissue engineering strategies for successful tendon regeneration.

肌腱损伤是一种常见的肌肉骨骼疾病，其特征是肌腱的自然愈合能力有限，无法恢复其原有的结构和功能。基于肌腱干/祖细胞（TSPCs）的肌腱组织工程为肌腱损伤治疗提供了一种潜在的策略。TSPCs的功能调控受体内和体外微环境因素的影响。在这里，我们提供了到目前为止确定的各种TSPCs亚群的简要总结。此外，我们还探讨了目前TSPCs体内微环境的研究进展。值得注意的是，我们首先引入了“退化回路”的概念，该概念强调了肌腱微环境与TSPCs之间复杂的相互作用。在此基础上，我们提出了“重塑生态位-破坏退行性循环-肌腱愈合”的理论和策略框架，以实现有效的肌腱再生。此外，我们还概述了通过操纵体外和体内微环境来调节TSPCs扩增和分化的最新进展。最后，提出了TSPCs亚群再生应用面临的挑战和相关前景。对不同TSPCs亚群及其微环境之间相互作用的更深层次的多尺度理解将极大地促进创新组织工程策略的发展，从而成功地实现肌腱再生。

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引用次数: 0

Development of a primary hepatocyte-based preclinical spheroid model system for the analysis of Phase I and Phase II enzyme activity in vitro 开发一种基于原代肝细胞的临床前球体模型系统，用于体外分析I期和II期酶活性

Q1 Medicine

Engineered regeneration

Pub Date : 2026-01-01 DOI: 10.1016/j.engreg.2026.01.001

Kenichi Arai , Kazuya Fukuhara-Obonai , Soichi Ishimaru , Nobuhiko Kojima , Tanveer Ahmad Mir , Takahiro Kitsuka , Masahiro Hosaka

Hepatic spheroids formed by the spontaneous self-aggregation of hepatocytes maintain better liver function than two-dimensional (2D) monolayer cultures. Although structural polarity and intercellular adhesion can be maintained in hepatic spheroids, cell-extracellular matrix (ECM) interactions cannot be reproduced in spheroid-based models. In this study, we leveraged customizable ECM component and fabricated hepatic by injecting a cell suspension supplemented with primary mouse hepatocytes and Matrigel into a high-density methylcellulose (MC) solution. Amongst other findings, gene expression analysis of hepatic spheroid aggregates containing Matrigel revealed elevated levels of drug-metabolizing enzymes (Phase I and II) and transporters (compared to spheroids without Matrigel). Furthermore, the induction of drug metabolism enzymes and activity in hepatic spheroids containing Matrigel also increased compared to those without Matrigel. Lastly, we demonstrated that hepatic spheroids containing Matrigel can maintain liver function by increasing HNF4α through activation of Hippo signaling. Overall, our results indicate that high-performance hepatic spheroids containing Matrigel can maintain liver function through cell-cell and cell-ECM interactions and can be used to increase the efficiency of drug screening.

由肝细胞自发自聚集形成的肝球体比二维（2D）单层培养维持更好的肝功能。虽然结构极性和细胞间粘附可以在肝球体中维持，但细胞-细胞外基质（ECM）相互作用不能在基于球体的模型中重现。在这项研究中，我们利用可定制的ECM组件，通过将含有原代小鼠肝细胞和Matrigel的细胞悬浮液注射到高密度甲基纤维素（MC）溶液中来制造肝脏。在其他发现中，含有Matrigel的肝球状聚集体的基因表达分析显示药物代谢酶（I期和II期）和转运蛋白水平升高（与不含Matrigel的球体相比）。此外，与不含Matrigel的肝球体相比，含有Matrigel的肝球体对药物代谢酶的诱导作用和活性也有所增加。最后，我们证明了含有Matrigel的肝球体可以通过激活Hippo信号通过增加HNF4α来维持肝功能。总之，我们的研究结果表明，含有Matrigel的高性能肝球体可以通过细胞间和细胞- ecm相互作用维持肝功能，并可用于提高药物筛选的效率。

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引用次数: 0

Integrating bioprinted oral epithelium with millifluidics for fluorouracil perfusion and Fusobacterium infection to bioengineer oral mucositis-on-a-chip 将生物打印的口腔上皮与微流体相结合，用于氟尿嘧啶灌注和梭杆菌感染，以生物工程口腔粘膜炎芯片

Q1 Medicine

Engineered regeneration

Pub Date : 2025-03-01 DOI: 10.1016/j.engreg.2025.02.001

Tien T.T. Truong , Toan V. Phan , Yamin Oo , Ladawan Sariya , Risa Chaisuparat , Silvia Scaglione , Glauco R. Souza , Supansa Yodmuang , Catherine H.L. Hong , Kai Soo Tan , Waranyoo Phoolcharoen , Oranart Matangkasombut , João N. Ferreira

Oral mucositis (OM) remains a painful complication of anticancer chemotherapy (CT), tending to progress in severity in the presence of Fusobacterium nucleatum (Fn). Yet, no effective therapy exists to suppress OM since in vitro models mimicking CT-induced OM are lacking, halting the discovery of new drugs. Here, we developed an integrated millifluidic in vitro tissue culture system for OM disease modeling. This bioengineered system integrates magnetically bioassembled oral epithelium sheets with millifluidics for CT-based 5-fluorouracil perfusion and Fn infection to model CT-induced OM. After modeling OM with all pro-inflammatory hallmarks, we were able to suppress OM with our in-house plant-produced epidermal growth factor (P-EGF), a well-known re-epithelialization cue. Thus, this the first instance where a milifluidic system enabled OM modeling in the presence of CT drug perfusion and Fn infection. This bioengineered system is a novel tool for drug discovery as it propelled P-EGF as a promising therapy for OM.

口腔黏膜炎（OM）仍然是抗癌化疗（CT）的一种痛苦的并发症，在核梭杆菌（Fn）存在的情况下，其严重程度趋于恶化。然而，由于缺乏模拟ct诱导的OM的体外模型，没有有效的治疗方法来抑制OM，阻碍了新药的发现。在这里，我们开发了一种集成的微流体体外组织培养系统，用于OM疾病建模。该生物工程系统将磁性生物组装口腔上皮片与微流体结合，用于基于ct的5-氟尿嘧啶灌注和Fn感染，以模拟ct诱导的OM。在模拟了具有所有促炎特征的OM后，我们能够用我们的内部植物产生的表皮生长因子（P-EGF）抑制OM，这是一种众所周知的再上皮化线索。因此，这是在CT药物灌注和Fn感染的情况下，毫流体系统实现OM建模的第一个实例。这种生物工程系统是药物发现的新工具，因为它推动了P-EGF作为一种有希望的治疗OM的方法。

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引用次数: 0

Force induces axon growth in inhibitory conditions 力在抑制条件下诱导轴突生长

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.05.003

Elena Capitanini , Laura Talarico , Sara De Vincentiis , Chiara Giacomelli , Sara Vitolo , Lorenzo Da Palmata , Laura Marchetti , Elisabetta Ferraro , Maria Letizia Trincavelli , Vittoria Raffa

Axon navigation is guided by spatial patterns of chemical and physical cues in the developing central nervous system. Following injury, these patterns are disrupted, the microenvironment evolves rapidly, and inhibitory molecules create a barrier to the regeneration of severed axons. We have recently developed a technology called nano-pulling designed to stimulate axon growth and regeneration by modulating neuronal mechanotransduction. In this paper, we demonstrate that nano-pulling can induce axon growth in hippocampal neurons even in the presence of repulsive cues, such as chondroitin sulfate proteoglycans, semaphorin 3A, microglial activation, and pro-inflammatory cytokines. Nano-pulling can also enhance the elongation of neural processes in neural progenitors transplanted into an organotypic spinal cord injury model that mimics the tissue complexity and inflammation seen in in vivo models. Our data suggest that nano-pulling could be used as a strategy to manipulate axon growth, overcoming certain extrinsic inhibitory factors.

轴突导航是由发育中的中枢神经系统的化学和物理线索的空间模式引导的。损伤后，这些模式被破坏，微环境迅速进化，抑制分子对断裂轴突的再生产生障碍。我们最近开发了一种叫做纳米拉的技术，旨在通过调节神经元的机械转导来刺激轴突的生长和再生。在本文中，我们证明了纳米拉力可以诱导海马神经元轴突生长，即使存在排斥信号，如硫酸软骨素蛋白聚糖、信号蛋白3A、小胶质细胞激活和促炎细胞因子。纳米牵拉还可以增强神经祖细胞移植到器官型脊髓损伤模型中的神经过程的伸长，该模型模仿体内模型中的组织复杂性和炎症。我们的数据表明，纳米拉力可以作为一种策略来操纵轴突的生长，克服某些外在的抑制因素。

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引用次数: 0

The microenvironment in atherosclerosis: molecular regulation mechanism and immunotherapy 动脉粥样硬化中的微环境：分子调控机制和免疫治疗

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.07.002

Xiaoyu Teng , Qinlian Jiao , Yidan Ren , Xin Su , Zigan Li , Yuxuan Cai , Tangbin Hu , Maoxiao Feng , Xiaoyan Liu , Ming Xia , Jun Tai , Yana Zhang , Yunshan Wang , Mo Wang

Atherosclerosis is a chronic inflammatory disease closely linked to immune dysregulation. The immune microenvironment within atherosclerotic lesions is highly complex, involving diverse innate and adaptive immune cells and their intricate crosstalk. These immune interactions collectively contribute to plaque formation, progression, and destabilization. This review comprehensively examines the roles of key immune cell populations—including macrophages, dendritic cells (DCs), neutrophils, mast cells, natural killer (NK) cells, T cells, and B cells—in regulating inflammation, foam cell formation, and lesion stability. Special attention is given to intercellular regulatory circuits such as the Th1–M1 feedback loop, the OX40L–Th17 axis, and DC–T–NK amplification loops. Furthermore, the review highlights the influence of immunometabolic reprogramming on immune cell function and plaque phenotype, illustrating how metabolic states shape inflammatory outcomes. It also discusses the contribution of key signaling pathways—including Toll-like receptors (TLRs), the NOD-like receptor protein 3 (NLRP3) inflammasome, and proprotein convertase subtilisin/kexin type 9 (PCSK9)—to atherosclerotic inflammation and plaque vulnerability. Advances in immunotherapy are also reviewed, including anti-inflammatory agents such as colchicine and canakinumab, as well as emerging vaccine strategies targeting lipid metabolism and vascular inflammation.

A deeper understanding of immune cell interplay and signaling dynamics in atherosclerosis will provide a foundation for developing more effective, multi-targeted immunotherapeutic interventions. Future research should aim to refine these strategies to maximize efficacy and safety, with the goal of reducing the global burden of atherosclerotic cardiovascular disease.

动脉粥样硬化是一种与免疫失调密切相关的慢性炎症性疾病。动脉粥样硬化病变内的免疫微环境是高度复杂的，涉及多种先天和适应性免疫细胞及其复杂的相互作用。这些免疫相互作用共同促进斑块的形成、进展和不稳定。本文综述了包括巨噬细胞、树突状细胞（dc）、中性粒细胞、肥大细胞、自然杀伤细胞（NK）、T细胞和B细胞在内的关键免疫细胞群在调节炎症、泡沫细胞形成和病变稳定性中的作用。特别关注细胞间调节回路，如Th1-M1反馈回路、OX40L-Th17轴和DC-T-NK放大回路。此外，该综述强调了免疫代谢重编程对免疫细胞功能和斑块表型的影响，说明了代谢状态如何影响炎症结果。它还讨论了关键信号通路的贡献，包括toll样受体（TLRs）， nod样受体蛋白3 （NLRP3）炎症小体和蛋白转化酶枯草杆菌素/酮蛋白9 （PCSK9）对动脉粥样硬化炎症和斑块易感性的影响。免疫治疗的进展也进行了回顾，包括抗炎药，如秋水仙碱和canakinumab，以及针对脂质代谢和血管炎症的新兴疫苗策略。对动脉粥样硬化中免疫细胞相互作用和信号动力学的深入了解将为开发更有效的多靶向免疫治疗干预提供基础。未来的研究应旨在完善这些策略，以最大限度地提高疗效和安全性，以减少动脉粥样硬化性心血管疾病的全球负担。

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引用次数: 0

Current advances and prospects in biomaterials-guided tools for liver organoids research 生物材料导向类肝器官研究工具的现状与展望

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.07.004

Sana Ahmed , Eman Alshehri , Sarah Nazneen , Fayrouz Attia , Dalia Obeid , Hanan Almuzaini , Alaa Alzahrani , Jahan Salma , Iriya Fujitsuka , Abdullah M. Assiri , Dieter C. Broering , Raja Chinnappan , Ahmed Yaqinuddin , Tanveer Ahmad Mir

Liver is the largest solid organ in the human body engaged in an array of critical physiological activities that primarily support metabolism, digestion, nutrient storage, detoxification. Liver dysfunction due to disease or surgical intervention often leads to severe life-threatening complications or death in humans. Therefore, in vitro liver models that mimic key functional characteristics are considered a reliable option for the study of liver diseases and the development of new therapeutic agents. Furthermore, they can overcome the limitations of conventional monolayer cultures and animal related experiments in assessing the response of new therapeutic agents and drug molecules. In recent years, the emergence and advancement of organoid technology has greatly facilitated the development of reliable in vitro liver models for a variety of biomedical and pharmacological applications. However, organoid culture primarily relies on tumor-derived extracellular matrix, such as Matrigel, which pose challenges due to its xenogeneic nature and variable composition. Therefore, creating organoid models using Matrigel-free hydrogel materials could significantly improve the outcomes of regenerative medicine and experimental studies. In this review, we provide an overview of rapidly evolving biomaterials for organoid research. We then outline preparation methods and the most relevant studies applying different hydrogels for engineering liver organoid models. Finally, we discuss the challenges, future perspectives, and opportunities of hydrogels in engineering next-generation liver organoid models for translational applications.

肝脏是人体最大的固体器官，参与一系列重要的生理活动，主要是支持新陈代谢、消化、营养储存和解毒。由于疾病或手术干预引起的肝功能障碍往往导致严重的危及生命的并发症或死亡。因此，模拟关键功能特征的体外肝脏模型被认为是肝脏疾病研究和新治疗剂开发的可靠选择。此外，它们可以克服传统单层培养和动物相关实验在评估新治疗剂和药物分子反应方面的局限性。近年来，类器官技术的出现和进步极大地促进了可靠的体外肝脏模型的发展，用于各种生物医学和药理学应用。然而，类器官培养主要依赖于肿瘤来源的细胞外基质，如Matrigel，由于其异种性和可变成分，这带来了挑战。因此，使用不含matrigel的水凝胶材料创建类器官模型可以显著改善再生医学和实验研究的结果。在这篇综述中，我们提供了快速发展的生物材料类器官的研究综述。然后，我们概述了制备方法和应用不同水凝胶用于工程肝类器官模型的最相关研究。最后，我们讨论了水凝胶在工程下一代肝类器官模型转化应用中的挑战、未来前景和机遇。

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引用次数: 0

Corrigendum to “Conductive PS inverse opals for regulating proliferation and differentiation of neural stem cells” [Engineered Regeneration 4 (2023) 214-221] “用于调节神经干细胞增殖和分化的导电PS逆蛋白石”的勘误表[工程再生4 (2023)214-221]

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.12.001

Yangnan Hu , Han Zhang , Hao Wei , Menghui Liao , Xiaoyan Chen , Jiayue Xing , Lian Duan , Cuntu Cheng , Weicheng Lu , Xuechun Yang , Peina Wu , Huan Wang , Jingdun Xie , Renjie Chai

引用次数: 0

Comparison of two hemostatic skin adhesive dressings, incorporating multi-metal bioactive glass 两种含有多金属生物活性玻璃的止血皮肤粘合敷料的比较

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2024.06.003

Melina Ghasemian , Neda Alasvand , Ali Samadikuchaksaraei , Hajir Bahrami , Mahmoud Azami , Farzad Ramroudi , Soheila Naderi Gharahgheshlagh , Hajar Nasiri , Soroush Taherkhani , Peiman Brouki Milan

Current bioadhesive dressings, though potential in wound care, often exhibit inadequate adhesion and lack essential properties for optimal wound healing, such as being antibacterial, hemostatic, and angiogenic. While various scaffolds containing natural adhesive molecules such as 3,4-dihydroxyphenyl-L-alanine (DOPA) and tannic acid (TA) have been individually assessed, the comparison of adhesives containing these molecules are scarcely studied. This study addresses these limitations by developing two innovative composite hydrogel adhesives, based on DOPA and TA, which are integrated with novel multi-metal bioactive glass nanoparticles (BGNs). A comprehensive comparison of their properties was conducted to evaluate their potential in improving wound healing outcomes.

BGNs were synthesized using sol-gel approach, yielding an amorphous and porous structure. Incorporation of 10 % w/w BGNs with uniform distribution enhanced the mechanical and adhesive properties of both hydrogels, with TA-based dressings demonstrating superior performance. While both dressings demonstrated biocompatibility and hemocompatibility, TA-based adhesive outperformed DOPA-based adhesive in cell viability and antibacterial activity against Staphylococcus aureus and Escherichia coli, while DOPA-based composites showed better in vitro angiogenic and hemostatic capabilities.

Regarding in vivo investigations, conducted on mice model of full-thickness skin wounds, DOPA- incorporated adhesive dressing which contained 10 % BGN exhibited slightly superior performance in re-epithelialization, collagen formation and blood vessel density, indicating its potential for acute wound healing applications.

目前的生物胶粘剂敷料，虽然在伤口护理方面有潜力，但往往表现出不充分的粘连性，缺乏最佳伤口愈合的基本特性，如抗菌、止血和血管生成。虽然已经对含有3,4-二羟基苯基- l-丙氨酸（DOPA）和单宁酸（TA）等天然黏合剂分子的各种支架进行了单独评估，但很少对含有这些分子的黏合剂进行比较研究。本研究通过开发两种基于DOPA和TA的创新型复合水凝胶粘合剂来解决这些局限性，这两种粘合剂与新型多金属生物活性玻璃纳米颗粒（BGNs）相结合。对它们的性能进行了全面的比较，以评估它们在改善伤口愈合结果方面的潜力。采用溶胶-凝胶法合成了BGNs，得到了非晶多孔结构。10% w/w均匀分布的BGNs的加入增强了这两种水凝胶的力学和粘合性能，其中以ta为基础的敷料表现出更好的性能。虽然两种敷料都表现出生物相容性和血液相容性，但ta基粘合剂在细胞活力和对金黄色葡萄球菌和大肠杆菌的抗菌活性方面优于dopa基粘合剂，而dopa基复合材料则表现出更好的体外血管生成和止血能力。在小鼠全层皮肤创面模型的体内实验中，含有10% BGN的DOPA-粘接剂敷料在再上皮化、胶原形成和血管密度方面表现出稍好的性能，提示其在急性创面愈合方面的应用潜力。

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引用次数: 0

Advances in smart hybrid scaffolds: A strategic approach for regenerative clinical applications 智能混合支架的进展：再生临床应用的战略方法

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.02.002

Ahsan Riaz Khan , Amol D. Gholap , Navdeep Singh Grewal , Zhang Jun , Mohammad Khalid , Hai-Jun Zhang

The emergence of innovative 3D-printed hybrid scaffolds is transforming the landscape of tissue engineering by effectively addressing various regenerative clinical challenges. These scaffolds, which combine the advantageous properties of metals, polymers, and ceramics, surpass the limitations associated with single-material constructs. This review provides a comprehensive analysis of the applications of hybrid scaffolds in cardiology, orthopedics, and neural tissue regeneration, highlighting their role in advancing biomimetics, accelerating wound healing, enabling targeted drug delivery, and facilitating tumor therapy. Critical factors such as biomechanical compatibility, bioactivity, degradation rates, and mechanical integrity are critically evaluated following scaffold integration into host tissues. Additionally, nano-topographical features are explored to assess scaffold performance and cellular interactions. Key architectural parameters such as porosity, pore size, and interconnectivity are analyzed for their biological implications in physiological conditions. Furthermore, the investigation extends to smart scaffolds that incorporate stimuli-responsive mechanisms through 4D printing and shape memory polymers, which mimic the complex and dynamic properties of living tissues in response to various stimuli. The review concludes by highlighting the significance of integrating stimuli-responsive characteristics as a fourth dimension in hybrid scaffolds, thereby enhancing their potential for advanced clinical applications.

创新的3d打印混合支架的出现，通过有效地解决各种再生临床挑战，正在改变组织工程的格局。这些支架结合了金属、聚合物和陶瓷的优点，超越了单一材料结构的局限性。本文综述了混合支架在心脏病学、骨科和神经组织再生中的应用，重点介绍了它们在推进仿生、加速伤口愈合、实现靶向药物传递和促进肿瘤治疗方面的作用。关键因素，如生物力学相容性、生物活性、降解率和机械完整性，在支架整合到宿主组织后进行严格评估。此外，纳米形貌特征的探讨，以评估支架的性能和细胞相互作用。关键的建筑参数，如孔隙度，孔径和互联性分析其在生理条件下的生物学意义。此外，该研究扩展到智能支架，通过4D打印和形状记忆聚合物结合刺激响应机制，模仿活组织在各种刺激下的复杂和动态特性。综述最后强调了将刺激反应特性作为混合支架的第四个维度的重要性，从而增强了它们在高级临床应用中的潜力。

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引用次数: 0

Decellularized tissue-specific hydrogels support an engineered salivary gland within a microfluidic platform 脱细胞组织特异性水凝胶在微流控平台内支持工程唾液腺

Q1 Medicine

Engineered regeneration

Pub Date : 2025-01-01 DOI: 10.1016/j.engreg.2025.11.002

Chau B. Lam , Toan V. Phan , Sawang Kesdangsakonwut , Padet Tummaruk , Risa Chaisuparat , Supansa Yodmuang , Jae-Yol Lim , Joao N. Ferreira

Mucoepidermoid carcinoma (MEC) is a rare malignancy of the salivary gland (SG) that poses significant treatment challenges. This highlights the need for in vitro cancer modeling platforms towards anti-cancer drug screening applications. Emerging organ-on-a-chip (OoC) microfluidic technologies represent promising new approach methodologies (NAMS) and a real alternative to animal testing. While tissue-specific decellularized extracellular matrix (ECM) can recapitulate in vivo-like microenvironments, its application in SG-on-a-chip (SGoC) is still underexplored. This study developed an injectable porcine decellularized submandibular gland (dSMG) hydrogel for bioengineering an SG MEC tissue chip. dSMG was prepared using a chemical and enzymatic decellularization process with 0.1 % or 1 % sodium dodecyl sulfate (SDS). Both treatments effectively removed DNA content while preserving key ECM components, including collagens, glycoproteins, and mucins. Proteomic analysis revealed that 1 % SDS-treated dSMG contained a greater abundance of ECM components involved in matrix assembly and cell-ECM interactions compared to the 0.1 % group. The 1 % SDS-treated dSMG was subsequently digested with a pepsin-based buffer to form hydrogels. At 5 mg/mL, dSMG hydrogel exhibited nanofibrous architecture, thermo-responsive gelation, injectability into microfluidic devices, and minimal batch-to-batch biological variations. In static conditions, dSMG hydrogel significantly enhanced SG cell viability and mitochondria-dependent proliferation compared to Matrigel. Under gravity-driven flow, dSMG hydrogel promoted a ductal phenotype on human SG MEC cells, unlike on Matrigel. Additionally, dSMG hydrogel supported cholinergic-specific signaling and functional activity. These findings demonstrate the potential of dSMG hydrogel as a physiologically relevant matrix for SG cancer modeling towards drug screening applications in SGoC microfluidic systems.

黏液表皮样癌（MEC）是一种罕见的涎腺恶性肿瘤（SG），对治疗提出了重大挑战。这突出了对抗癌药物筛选应用的体外癌症建模平台的需求。新兴的器官芯片（OoC）微流控技术代表了有前途的新方法方法（NAMS）和动物试验的真正替代方案。虽然组织特异性脱细胞细胞外基质（ECM）可以在体内样微环境中重现，但其在芯片上的应用仍未得到充分探索。本研究研制了一种可注射的猪下颌骨去细胞腺（dSMG）水凝胶，用于生物工程和sgmec组织芯片。采用0.1%或1%十二烷基硫酸钠（SDS）的化学脱细胞和酶解脱细胞工艺制备了dSMG。两种处理都有效地去除了DNA含量，同时保留了关键的ECM成分，包括胶原、糖蛋白和粘蛋白。蛋白质组学分析显示，与0.1%组相比，1% sds处理的dSMG含有更丰富的参与基质组装和细胞-ECM相互作用的ECM成分。1% sds处理过的dSMG随后用胃蛋白酶缓冲液消化形成水凝胶。当浓度为5 mg/mL时，dSMG水凝胶表现出纳米纤维结构、热响应性凝胶、可注射到微流体装置中，并且批间生物变异最小。在静态条件下，与Matrigel相比，dSMG水凝胶显著提高了SG细胞的活力和线粒体依赖性增殖。在重力驱动下，dSMG水凝胶促进了人SG MEC细胞的导管表型，这与Matrigel不同。此外，dSMG水凝胶支持胆碱能特异性信号传导和功能活性。这些发现证明了dSMG水凝胶作为sgc微流控系统中sgc癌症建模和药物筛选的生理相关基质的潜力。

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引用次数: 0