Coating the cell surface with adhesive polymers: a strategy to enhance cell adhesion

用粘附聚合物涂覆细胞表面：增强细胞粘附的策略

• 批准号: EP/X037622/1
• 负责人: Maria Chiara Arno
• 金额: $ 56.04万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX037622%2F1
• 关键词: Coating; cell; surface; adhesive; polymers

Developing polymeric coatings for mammalian cells offers the opportunity to tune the chemical and physical environment at the cell surface. This emerging technology has the potential to enable significant advances in the field of cell-based therapies and push forward their clinical application in regenerative medicine. One of the most established methodologies to achieve a polymeric coating around cells relies on the use of materials with an overall positive charge that can interact with the anionic cell surface. However, this approach has been proved to be inadequate for the coating of single cells, as positively charged polymers can disrupt the cell membrane and consequently induce cell death. Similarly, the susceptibility of mammalian cells to mechanical and chemical stress has also limited the covalent conjugation of polymer chains through functionalities already present at the cell surface, hence restricting the chemistry available to achieve a homogeneous and long-lasting cell coating. Nevertheless, recent advances have demonstrated that bio-orthogonal click strategies can be used to introduce exogenous functional groups at the cell surface that can be exploited for polymer conjugation. While these strategies have undoubtedly advanced the field of cell engineering, achieving a homogeneous polymer coating with tuneable properties that is able to control cell behaviour remains an unmet challenge. Importantly, investigating how polymer composition and density of conjugation can be exploited to modulate cell behaviour is essential to fully realise the potential of cell coating strategies in the field of tissue engineering and beyond. This is exactly what this project intends to achieve. By developing robust methodologies for single cell coating, we aim to provide a platform to control cell adhesion with the extracellular matrix and surrounding tissue. This is particularly relevant in tissue regeneration, where cells with regenerative potential (tissue-specific or staminal cells) are injected directly into the target tissue and vasculature to promote tissue growth. Often, cell attachment to the existing tissue is low, mainly as a result of inefficient adhesion of transplanted cells to the surrounding environment, which in turn leads to their programmed death and clearance by the circulatory system. In this project, we will use human liver cells as a model system that will allow us to develop the chemistry and deliver fundamental understanding on the polymer structure, molecular weight, and density of conjugation that are needed to achieve a homogeneous cell coating. This cell type has shown great promise for the development of targeted cell-based therapies for liver regeneration. Using liver as a model, our goal is to develop a versatile coating platform that can be applied to a wide range of cells, advancing the field of cell-based therapies for tissue regeneration.The project represents a priority area for the UK and aligns strongly with the EPSRC's prosperity outcomes (Healthy Nation) and the Healthcare Technologies grand challenges. It also tallies with the United Nations (UN) Sustainable Development Goals, specifically Goal 3: 'Ensure healthy lives and promote well-being for all at all ages.'

开发用于哺乳动物细胞的聚合物涂层提供了调整细胞表面的化学和物理环境的机会。这项新兴技术有可能在细胞疗法领域取得重大进展，并推动其在再生医学中的临床应用。在细胞周围实现聚合物涂层的最成熟的方法之一依赖于使用具有可与阴离子细胞表面相互作用的总正电荷的材料。然而，这种方法已被证明不适合单细胞的包被，因为带正电荷的聚合物可以破坏细胞膜，从而诱导细胞死亡。类似地，哺乳动物细胞对机械和化学应力的敏感性也限制了聚合物链通过细胞表面已经存在的官能团的共价缀合，因此限制了可用于实现均匀和持久的细胞涂层的化学。然而，最近的进展已经证明，生物正交点击策略可用于在细胞表面引入外源性官能团，其可用于聚合物缀合。虽然这些策略无疑推动了细胞工程领域的发展，但实现具有可调特性的均匀聚合物涂层，从而能够控制细胞行为，仍然是一个尚未解决的挑战。重要的是，研究如何利用聚合物组合物和缀合密度来调节细胞行为对于充分实现组织工程领域及其他领域的细胞包被策略的潜力至关重要。这正是这个项目想要实现的。通过开发单细胞包被的稳健方法，我们的目标是提供一个平台来控制细胞与细胞外基质和周围组织的粘附。这在组织再生中特别相关，其中将具有再生潜力的细胞（组织特异性或雄蕊细胞）直接注射到靶组织和脉管系统中以促进组织生长。通常，细胞对现有组织的附着是低的，主要是由于移植细胞对周围环境的粘附效率低下，这反过来又导致它们的程序性死亡和循环系统的清除。在这个项目中，我们将使用人类肝细胞作为模型系统，这将使我们能够开发化学，并提供对实现均匀细胞涂层所需的聚合物结构，分子量和缀合密度的基本理解。这种细胞类型在开发用于肝再生的靶向细胞疗法方面显示出巨大的前景。以肝脏为模型，我们的目标是开发一种可应用于多种细胞的多功能涂层平台，推进基于细胞的组织再生疗法领域。该项目代表了英国的优先领域，并与EPSRC的繁荣成果（健康国家）和医疗保健技术的重大挑战紧密结合。它也符合联合国可持续发展目标，特别是目标3：“确保健康的生活，促进所有年龄段所有人的福祉。'