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——所有其他类型细胞的前体细胞——为医学的未来开辟了全新的可能性，因为它们可以被鼓励转化为不同类型的有用生长组织。特别是，干细胞技术具有促进体内关节修复、神经组织再生、骨骼重建和心血管修复的潜力。更复杂且具有潜在价值的是使用干细胞在体外培养整个器官，适合移植到患者体内。这可能会满足许多等待死亡的患者对器官的未满足的需求。此外，由于干细胞的使用，这将提供适合患者免疫系统的器官，防止器官排斥，从而避免与抗排斥药物相关的巨额成本。该项目探索了一种新型软凝胶相材料，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，因此具有不同的特性。因此，生长的生物组织在材料的不同区域中表现不同。虽然创建与组织生长相容的简单凝胶相对简单，但对多个组件进行图案化以引导干细胞在材料的不同区域做不同的事情要困难得多。使用聚合物凝胶为组织生长形成图案凝胶的目标已经取得了进展，但我们的方法利用了自组装小分子凝胶剂，它有可能更具可编程性和响应性。光将用于图案凝胶组装，将我们的技术与现有的聚合物凝胶相结合，以创建具有刚性和软域的连贯图案材料。预计此类材料将鼓励干细胞分化成不同类型，例如干细胞。骨头在较硬的区域，脂肪在较软的区域。然后，生物活性剂（例如组织生长因子）将被纳入我们新材料的特定领域。这些药物的受控释放将能够影响正在生长的组织——原则上，这可以通过空间和时间控制来实现。通过这种方式，生长的细胞在特定位置的选定时间受到特定刺激。导电单元也将被嵌入到特定的凝胶域中，以便导电通路只能在凝胶的特定区域中组装。我们预计这些传导途径将使生长的组织培养物的一部分能够在选定的时间点以选择性的方式受到电刺激——可能鼓励细胞以独特且可控的方式发育。多域凝胶的开发具有高度创新性，该项目需要解决许多重要的挑战。将发展和控制单一材料中的多个成分的基本理解。将活性剂掺入多域凝胶中以实现空间和时间上的受控释放，以及在此类凝胶内开发传导途径以前从未实现过。因此，该项目构成了多域凝胶技术的重大变革。我们相信这种方法可能会彻底改变组织工程方法，我们将展示其潜力。利用对软材料的超分子理解来控制它们与活性剂以及在其直接环境中生长的生物有机体相互作用的方式，通过使用超分子化学原理与生命系统生物学相结合，使定向组装的 EPSRC 化学“重大挑战”远远超出了其当前的化学最先进水平。

项目成果

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

Self-assembled low-molecular-weight gelator injectable microgel beads for delivery of bioactive agents.

自组装的低分子量凝胶剂可注射的微凝胶珠，用于递送生物活性剂。

• DOI: 10.1039/d0sc06296k
• 发表时间: 2021-02-02
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Piras CC;Kay AG;Genever PG;Smith DK
• 通讯作者: Smith DK