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.'

为哺乳动物细胞开发聚合物涂层提供了调节细胞表面化学和物理环境的机会。这项新兴技术有潜力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整体正电荷的材料。然而，这种方法已被证明不足以涂覆单个细胞，因为带正电荷的聚合物会破坏细胞膜，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有的官能团的共价缀合，从而限制了可用于实现均匀且持久的细胞涂层的化学作用。然而，最近的进展表明，生物正交点击策略可用于在细胞表面引入可用于聚合物缀合的外源官能团。虽然这些策略无疑推进了细胞工程领域的发展，但实现具有可调节特性、能够控制细胞行为的均质聚合物涂层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成和缀合密度来调节细胞行为对于充分发挥细胞涂层策略在组织工程及其他领域的潜力至关重要。这正是该项目想要实现的目标。通过开发稳健的单细胞涂层方法，我们的目标是提供一个控制细胞与细胞外基质和周围组织粘附的平台。这在组织再生中尤其重要，其中具有再生潜力的细胞（组织特异性细胞或雄蕊细胞）被直接注射到目标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力较低，主要是由于移植细胞与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了解。这种细胞类型在开发基于细胞的靶向肝再生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，并与英国紧密结合EPSRC 的繁荣成果（健康国家）和医疗保健技术的巨大挑战。它还符合联合国 (UN) 可持续发展目标，特别是目标 3：“确保健康的生活并促进各年龄段所有人的福祉。”