Multi-Domain Self-Assembled Gels: From Multi-Component Materials to Spatial and Temporal Control of Multi-Component Biology

多域自组装凝胶：从多组分材料到多组分生物学的时空控制

• 批准号: EP/P03361X/1
• 负责人: David Smith
• 金额: $ 45.84万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FP03361X%2F1
• 关键词: Multi; Domain; Self; Assembled; Gels

Stem cells - cells which are precursor cells to all other types of cells - open up radical new possibilities for the future of medicine as they can be encouraged to convert into different types of useful growing tissue. In particular, stem cell technology offers potential to encourage joint restoration, nerve tissue regeneration, bone reconstruction and cardiovascular repair in vivo. More complex, and potentially valuable, is the use of stem cells to grow whole organs ex vivo, suitable for transplantation into patients. This would potentially satisfy the unmet need for organs faced by many patients, who die waiting. Further, this would provide organs which, because of the use of stem cells, will be tailored to the patient's immune system preventing organ rejection, and hence avoiding the massive cost associated with anti-rejection medication. This project explores a new class of soft gel-phase materials which will be able to direct and control tissue growth in more precise and sophisticated ways than can currently be achieved. We will create multi-domain gels in which different regions of the material have different chemical compositions and hence different properties. As a result, growing biological tissue will behave differently in different domains of the material. Although creating simple gels which are compatible with tissue growth is relatively straightforward, patterning multiple components in order to direct stem cells to do different things in different regions of the material is much harder. Progress has been made towards the goal of patterning gels for tissue growth using polymer gels, but our approach makes use of self-assembling small-molecule gelators, which have the potential to be much more programmable and responsive. Light will be used to pattern gel assembly, combining our technology with established polymer gels to create coherent patterned materials which have both rigid and soft domains. It would be expected that such materials would encourage stem cells to differentiate into different types - e.g. bone on the harder domains and fat on the softer domains. Biologically active agents, such as tissue growth factors, will then be incorporated within specific domains of our new materials. The controlled release of these agents will then be able to influence the growing tissue - in principle, this can be achieved with both spatial and temporal control. In this way, the growing cells are exposed to specific stimuli at chosen times in specific locations. Conducting units will also be embedded into specific gel domains, so that conducting pathways can be assembled only in specific regions of the gel. We anticipate that these conducting pathways will enable parts of growing tissue culture to be electrically stimulated in a selective manner at a chosen time point - potentially encouraging cells to develop in unique and controllable ways.The development of multi-domain gels is highly innovative and a number of important challenges will need to be solved in this project. Fundamental understanding will develop and control over multiple components within a single material will be achieved. Incoporating active agents into multi-domain gels for spatially and temporally controlled release, and the development of conducting pathways within such gels have never previously been achieved. As such, this project constitutes a step-change in multi-domain gel technology. We believe this approach may revolutionise approaches to tissue engineering and we will demonstrate its potential. Employing a supramolecular understanding of soft materials in order to control the ways in which they interact both with active agents, and biological organisms growing in their direct environment, moves the EPSRC Chemistry 'Grand Challenge' of Directed Assembly well beyond its current chemical state-of-the art by using the principles of supramolecular chemistry to interface with living systems biology.

干细胞 - 是所有其他类型细胞的前体细胞的细胞 - 为医学的未来开辟了根本的新可能性，因为可以鼓励它们转化为不同类型的有用生长组织。特别是，干细胞技术在体内提供了鼓励关节恢复，神经组织再生，骨骼重建和心血管修复的潜力。更复杂的，潜在的有价值的是使用干细胞在体内生长整个器官，适合移植到患者中。这有可能满足许多​​等待死亡的患者面临的器官的未满足需求。此外，这将提供器官，由于使用干细胞，它将针对患者的免疫系统量身定制，从而防止器官排斥，从而避免了与抗排斥药物相关的大量成本。该项目探讨了一类新的软凝胶相材料，该材料将能够以比目前更精确和复杂的方式指导和控制组织生长。我们将创建多域凝胶，其中材料的不同区域具有不同的化学成分，因此具有不同的性质。结果，生长的生物组织在材料的不同结构域中的行为会有所不同。尽管创建与组织生长兼容的简单凝胶相对简单，但要模仿多个成分，以指导干细胞在材料的不同区域中做不同的事情，这要困难得多。为了使用聚合物凝胶制定组织凝胶的目标，取得了进展，但是我们的方法利用了自组装小分子凝胶剂，这有可能变得更加可编程和响应能力。光将用于模拟凝胶组件，将我们的技术与已建立的聚合物凝胶相结合，以创建具有刚性和软域的相干图案材料。可以预期，这种材料会鼓励干细胞分化为不同类型的类型 - 例如硬域上的骨头和较软的域上的脂肪。然后将在我们的新材料的特定域中纳入生物活性剂，例如组织生长因子。这些药物的受控释放将能够影响生长的组织 - 原则上，这可以通过空间和时间控制可以实现。这样，在特定位置，生长的细胞会在选定的时间暴露于特定的刺激中。传导单元也将嵌入特定的凝胶结构域中，因此只能在凝胶的特定区域组装传导途径。我们预计，这些导电途径将使生长的组织培养的一部分能够在选定的时间点以选择性的方式进行电刺激 - 潜在地鼓励细胞以独特和可控的方式发展。多域凝胶的发展具有高度创新性，并且在该项目中需要解决许多重要的挑战。将建立基本的理解并控制单个材料中的多个组件。将活性剂分为多域凝胶，以进行空间和时间控制的释放，并且以前从未实现过这种凝胶内的导电途径的发展。因此，该项目构成了多域凝胶技术的逐步变化。我们认为，这种方法可能会彻底改变组织工程的方法，我们将证明其潜力。通过对软材料进行超分子的理解，以控制它们与活性剂相互作用的方式，以及在其直接环境中生长的生物生物的相互作用，将EPSRC化学的定向组件的“大挑战”移动到其当前的化学化学范围内，通过使用与生物系统生物系统生物学相互作用的原理。

项目成果

Shaping and structuring supramolecular gels

• DOI: 10.1038/s41578-019-0111-6
• 发表时间: 2019-07-01
• 期刊: NATURE REVIEWS MATERIALS
• 影响因子: 83.5
• 作者: Chivers, Phillip R. A.;Smith, David K.
• 通讯作者: Smith, David K.

Combining gellan gum with a functional low-molecular-weight gelator to assemble stiff shaped hybrid hydrogels for stem cell growth

• DOI: 10.1039/d2ma00565d
• 发表时间: 2022-09-02
• 期刊: MATERIALS ADVANCES
• 影响因子: 5
• 作者: Piras，Carmen C.;Genever，Paul G.;Smith，David K.
• 通讯作者: Smith，David K.

Self-assembled gel tubes, filaments and 3D-printing with in situ metal nanoparticle formation and enhanced stem cell growth.

• DOI: 10.1039/d1sc06062g
• 发表时间: 2022-02-16
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Piras CC;Kay AG;Genever PG;Fitremann J;Smith DK
• 通讯作者: Smith DK

Self-Propelling Hybrid Gels Incorporating an Active Self-Assembled, Low-Molecular-Weight Gelator.

• DOI: 10.1002/chem.202102472
• 发表时间: 2021-10-19
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Piras CC;Smith DK
• 通讯作者: Smith DK

Self-Assembling Supramolecular Hybrid Hydrogel Beads

自组装超分子杂化水凝胶珠

• DOI: 10.1002/ange.201911404
• 发表时间: 2019
• 期刊: Angewandte Chemie
• 作者: Piras C