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文献精选 > 近年高分"类器官"研究（IF≥30，近5年）

Dynamic matrices with DNA-encoded viscoelasticity for cell and organoid culture. ​

文献信息 ​

DOI10.1038/s41565-023-01483-3
PMID37550574
期刊Nature nanotechnology
影响因子34.9
JCR 分区Q1
发表年份2023
被引次数28
关键词动态矩阵, DNA编码, 粘弹性, 细胞培养, 组织工程
文献类型Journal Article
ISSN1748-3387
页码1463-1473
期号18(12)
作者Yu-Hsuan Peng, Syuan-Ku Hsiao, Krishna Gupta, André Ruland, Günter K Auernhammer, Manfred F Maitz, Susanne Boye, Johanna Lattner, Claudia Gerri, Alf Honigmann, Carsten Werner, Elisha Krieg

一句话小结 ​

本研究开发了一种基于DNA文库的全合成水凝胶DyNAtrix，能够系统控制其粘弹性和机械特性，适用于三维细胞和类器官培养。DyNAtrix的优越性能如自愈合、高稳定性和可调降解性，使其在生物力学和组织工程领域具有重要应用潜力。

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动态矩阵 · DNA编码 · 粘弹性 · 细胞培养 · 组织工程

摘要 ​

三维细胞和类器官培养依赖于粘弹性基质的机械支撑。然而，常用的基质材料在关键的细胞指示特性方面缺乏控制能力。在此，我们报告了一种基于DNA文库的全合成水凝胶，它与超高分子量聚合物自组装，形成一种动态的DNA交联基质（DyNAtrix）。DyNAtrix能够通过改变DNA序列信息，对其粘弹性、热力学和动力学参数进行可计算预测和系统控制。可调的热激活使得哺乳动物细胞的均匀嵌入成为可能。有趣的是，压力松弛时间可以调节四个数量级，重现活组织的机械特性。DyNAtrix具有自愈合、可打印、高稳定性、细胞及血液相容性，以及可控降解的特性。基于DyNAtrix的人类间充质干细胞、全能干细胞、犬肾囊肿和人类滋养层类器官的培养显示出高生存率、增殖和形态发生。因此，DyNAtrix代表了一种可编程且多功能的精密基质，为生物力学、生物物理学和组织工程的先进方法提供了支持。

英文摘要 ​

Three-dimensional cell and organoid cultures rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack control over key cell-instructive properties. Here we report on fully synthetic hydrogels based on DNA libraries that self-assemble with ultrahigh-molecular-weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix). DyNAtrix enables computationally predictable and systematic control over its viscoelasticity, thermodynamic and kinetic parameters by changing DNA sequence information. Adjustable heat activation allows homogeneous embedding of mammalian cells. Intriguingly, stress-relaxation times can be tuned over four orders of magnitude, recapitulating mechanical characteristics of living tissues. DyNAtrix is self-healing, printable, exhibits high stability, cyto- and haemocompatibility, and controllable degradation. DyNAtrix-based cultures of human mesenchymal stromal cells, pluripotent stem cells, canine kidney cysts and human trophoblast organoids show high viability, proliferation and morphogenesis. DyNAtrix thus represents a programmable and versatile precision matrix for advanced approaches to biomechanics, biophysics and tissue engineering.

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主要研究问题 ​

  1. DyNAtrix在细胞和类器官培养中的具体应用有哪些，能否提供一些实验案例？
  2. 除了DNA交联矩阵，是否还有其他材料可以实现类似的可调节性和自愈合特性？
  3. 在使用DyNAtrix进行细胞培养时，如何优化其热激活过程以提高细胞嵌入的均匀性？
  4. DyNAtrix的可控降解特性如何影响细胞和类器官的长期生存和功能？
  5. 该技术在组织工程领域的潜在应用有哪些，特别是在再生医学和疾病模型构建方面？

核心洞察 ​

研究背景和目的 ​

三维细胞和类器官培养依赖于具有粘弹性的基质材料提供机械支持。然而，常用的基质材料在细胞指令性特性方面缺乏控制。本研究旨在开发一种新型的动态DNA交联基质（DyNAtrix），以实现对其粘弹性和其他关键物理特性的系统控制，从而提升细胞和类器官的培养效果。

主要方法/材料/实验设计 ​

本研究采用了一种基于DNA库的全合成水凝胶，能够与超高分子量聚合物自组装，形成动态交联基质。其主要步骤如下：

Mermaid diagram
  1. 材料合成：合成DNA功能化的超高分子量聚合物，并通过自由基聚合反应引入DNA链。
  2. 交联剂库设计：设计复杂的交联剂库，利用DNA序列的选择性结合来调节水凝胶的物理特性。
  3. 细胞培养：将人类间充质干细胞、诱导多能干细胞等嵌入DyNAtrix中进行培养。
  4. 性能评估：通过粘弹性、应力松弛等测试评估水凝胶的机械性能和细胞相容性。

关键结果和发现 ​

  1. DyNAtrix的物理特性：DyNAtrix展现出优异的自愈合性和可打印性，能够在低DNA浓度下形成稳定的水凝胶，其应力松弛时间可调范围达四个数量级，符合生物组织的机械特性。
  2. 细胞培养结果：在DyNAtrix中培养的细胞（如人类间充质干细胞和类器官）显示出高生存率和增殖能力。
  3. 生物相容性：DyNAtrix在血液相容性测试中表现出较低的单核细胞和血小板激活，显示出良好的生物相容性。

主要结论/意义/创新性 ​

DyNAtrix作为一种可编程和多功能的细胞培养基质，展示了DNA纳米技术在生物材料工程中的潜力。它的设计允许对材料的物理特性进行精确调控，为细胞和类器官培养提供了新的平台，能够更好地模拟生物体内环境。

研究局限性和未来方向 ​

尽管DyNAtrix表现出优异的性能，但仍存在以下局限性：

  • DNA浓度的经济性：虽然通过交联剂库的设计降低了DNA的使用量，但高浓度的DNA合成仍可能增加成本。
  • 细胞类型的适用性：目前的研究主要集中在几种细胞类型，未来需要探索DyNAtrix在更多细胞和类器官模型中的应用。

未来的研究方向包括：

  • 开发更低成本的DNA合成方法。
  • 探索DyNAtrix在临床应用中的潜力，如作为药物释放系统或医疗器械的涂层材料。

参考文献 ​

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  2. Substrate stress relaxation regulates cell spreading. - Ovijit Chaudhuri;Luo Gu;Max Darnell;Darinka Klumpers;Sidi A Bencherif;James C Weaver;Nathaniel Huebsch;David J Mooney - Nature communications (2015)
  3. A self-assembly pathway to aligned monodomain gels. - Shuming Zhang;Megan A Greenfield;Alvaro Mata;Liam C Palmer;Ronit Bitton;Jason R Mantei;Conrado Aparicio;Monica Olvera de la Cruz;Samuel I Stupp - Nature materials (2010)
  4. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. - Ovijit Chaudhuri;Luo Gu;Darinka Klumpers;Max Darnell;Sidi A Bencherif;James C Weaver;Nathaniel Huebsch;Hong-Pyo Lee;Evi Lippens;Georg N Duda;David J Mooney - Nature materials (2016)
  5. Design and evaluation of novel blood incubation systems for in vitro hemocompatibility assessment of planar solid surfaces. - U Streller;C Sperling;J Hübner;R Hanke;C Werner - Journal of biomedical materials research. Part B, Applied biomaterials (2003)
  6. Modular Design of Programmable Mechanofluorescent DNA Hydrogels. - Remi Merindol;Giovanne Delechiave;Laura Heinen;Luiz Henrique Catalani;Andreas Walther - Nature communications (2019)
  7. Demonstration that the shear force required to separate short double-stranded DNA does not increase significantly with sequence length for sequences longer than 25 base pairs. - K Hatch;C Danilowicz;V Coljee;M Prentiss - Physical review. E, Statistical, nonlinear, and soft matter physics (2008)
  8. Stress relaxing hyaluronic acid-collagen hydrogels promote cell spreading, fiber remodeling, and focal adhesion formation in 3D cell culture. - Junzhe Lou;Ryan Stowers;Sungmin Nam;Yan Xia;Ovijit Chaudhuri - Biomaterials (2018)
  9. Selective Nascent Polymer Catch-and-Release Enables Scalable Isolation of Multi-Kilobase Single-Stranded DNA. - Elisha Krieg;William M Shih - Angewandte Chemie (International ed. in English) (2018)
  10. DNA sequence-directed shape change of photopatterned hydrogels via high-degree swelling. - Angelo Cangialosi;ChangKyu Yoon;Jiayu Liu;Qi Huang;Jingkai Guo;Thao D Nguyen;David H Gracias;Rebecca Schulman - Science (New York, N.Y.) (2017)

引用本文的文献 ​

  1. Programmable and Reversible Integrin-Mediated Cell Adhesion Reveals Hysteresis in Actin Kinetics that Alters Subsequent Mechanotransduction. - Zheng Zhang;Hongyuan Zhu;Guoqing Zhao;Yunyi Miao;Lingzhu Zhao;Jinteng Feng;Huan Zhang;Run Miao;Lin Sun;Bin Gao;Wencheng Zhang;Zheng Wang;Jianfang Zhang;Ying Zhang;Hui Guo;Feng Xu;Tian Jian Lu;Guy M Genin;Min Lin - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
  2. Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor. - Congyi Shen;Jian Wang;Guangfeng Li;Shuyue Hao;Yan Wu;Peiran Song;Yafei Han;Mengmeng Li;Guangchao Wang;Ke Xu;Hao Zhang;Xiaoxiang Ren;Yingying Jing;Ru Yang;Zhen Geng;Jiacan Su - Bioactive materials (2024)
  3. Unraveling the Dual-Stretch-Mode Impact on Tension Gauge Tethers' Mechanical Stability. - Jingzhun Liu;Jie Yan - Journal of the American Chemical Society (2024)
  4. Advancing Synthetic Hydrogels through Nature-Inspired Materials Chemistry. - Bram G Soliman;Ashley K Nguyen;J Justin Gooding;Kristopher A Kilian - Advanced materials (Deerfield Beach, Fla.) (2024)
  5. The Role of Biophysical Factors in Organ Development: Insights from Current Organoid Models. - Yofiel Wyle;Nathan Lu;Jason Hepfer;Rahul Sayal;Taylor Martinez;Aijun Wang - Bioengineering (Basel, Switzerland) (2024)
  6. Y-switch: a spring-loaded synthetic gene switch for robust DNA/RNA signal amplification and detection. - Krishna Gupta;Elisha Krieg - Nucleic acids research (2024)
  7. DNA microbeads for spatio-temporally controlled morphogen release within organoids. - Cassian Afting;Tobias Walther;Oliver M Drozdowski;Christina Schlagheck;Ulrich S Schwarz;Joachim Wittbrodt;Kerstin Göpfrich - Nature nanotechnology (2024)
  8. ECM-mimicking composite hydrogel for accelerated vascularized bone regeneration. - Guanglong Li;Fei Gao;Donglei Yang;Lu Lin;Weijun Yu;Jiaqi Tang;Ruhan Yang;Min Jin;Yuting Gu;Pengfei Wang;Eryi Lu - Bioactive materials (2024)
  9. Recent Development of Fibrous Hydrogels: Properties, Applications and Perspectives. - Wen Luo;Liujiao Ren;Bin Hu;Huali Zhang;Zhe Yang;Lin Jin;Di Zhang - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2025)
  10. Acoustic virtual 3D scaffold for direct-interacting tumor organoid-immune cell coculture systems. - Han Shan;Maike Chen;Shuang Zhao;Xiongwei Wei;Mingde Zheng;Yixin Li;Qibo Lin;Zixi Jiang;Ziyan Chen;Chunlong Fei;Zhaoxi Li;Zeyu Chen;Xiang Chen - Science advances (2024)

... (18 更多 篇文献)

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