Exploiting nanoclay self-assembly for stem-cell driven tissue regeneration (Ext.)

这是该联谊会的延伸：“利用粘土纳米颗粒进行干细胞驱动的组织再生”干细胞通过再生患病或受损的组织，具有治愈多种疾病的巨大潜力。在人体从胚胎发育到损伤后的修复过程中，干细胞被来自局部微环境的高度协调的信号系统激活。生化分子浓度在空间和时间上变化的错综复杂的模式决定了组织如何生长以及它们采取的形式。如果我们要利用干细胞用于医疗保健的潜力，能够在体内传递和控制这些环境是至关重要的。我的研究目的是开发一种新型的水凝胶，由纳米尺寸(百万分之一毫米)的粘土颗粒形成，当被输送到人体内时，提供一个能够刺激和指导干细胞修复和再生病变或受损组织(如骨、软骨或皮肤)的环境。水凝胶是一种水含量非常高的凝胶。它们是输送干细胞的极佳候选者，因为它们允许营养物质的扩散，并且它们的基本物理特性模拟了细胞的自然环境。它们的主要缺点是，因为它们主要是由水形成的，它们往往不允许精确控制生化信号分子，而生化信号分子在指导干细胞如何运作方面是如此重要。某些纳米粘土颗粒还能够通过相互形成物理相互作用来形成水凝胶，从而形成一种锁定在水中的结构。它们还显示出非常不寻常和潜在有用的特性，即对生物分子具有极高的粘性。在过去的五年里，EPSRC资助了我的研究，探索如何利用这些特性在体内创造凝胶环境，从而激活干细胞形成骨骼。我们已经开发出可以注射到损伤部位的凝胶，以传递和结合骨生长因子，并以比先前报道的低得多的剂量刺激骨形成。然而，尽管前景看好，但我们注射大量凝胶和均匀混合的蛋白质的方法，与调节体内骨形成的精确浓度梯度相比，是相当粗糙的。然而，在这一探索过程中，我们发现了纳米粘土凝胶的一种新的意想不到的特性，这可能会使它们在刺激再生方面更加有效。除了能够保持混合生长因子，我们现在已经找到了一种简单的方法来精确地改变这些生物分子在凝胶本身中的排列。这是非常令人兴奋的，因为它可以让我们开始模仿在自然干细胞行为中如此重要的复杂模式。目前的资金将使我们能够探索这一特性，并测试将粘土生物分子图案应用于再生医学的方法。这是令人兴奋的，因为我们目前还不知道这些模式是如何形成的，为什么会形成，所以我们正在与专门研究纳米颗粒凝胶的物理学家合作，以获得对这种令人惊讶的行为的新见解。这也是令人兴奋的，因为它允许一种新的方法来探索生物分子模式在干细胞修复和再生中的作用。我们希望这项工作将使我们能够更有效、更可靠地利用干细胞治疗疾病的巨大潜力。

This is an extension of the Fellowship: "Harnessing clay nanoparticles for stem-cell driven tissue regeneration"Stem cells have great potential to cure a wide variety of conditions by regenerating diseased or damaged tissue. During the body's development from an embryo and during its repair after injury, stem cells are activated by a highly co-ordinated system of signals from the local micro-environment. Intricate patterns of spatially and temporally changing concentrations of biochemical molecules direct how tissues grow and the form that they take. Being able to deliver and control these environments in the body is vital if we are to harness the potential of stem cells for healthcare. The aim of my research is to develop a new type of hydrogel formed from nano-sized (1 millionth of a millimetre) clay particles that, when delivered into the body, provides an environment able to stimulate and direct stem cells to repair and regenerate diseased or damaged tissues such as bone, cartilage or skin. Hydrogels are gels with a very high water content. They are excellent candidates for delivering stem cells as they allow diffusion of nutrients and their basic physical properties mimic the cell's native environment. Their major drawback is that, because they are formed mainly of water, they do not tend to allow for the precise control of biochemical signalling molecules that is so important in directing how a stem cell functions. Certain nano-clay particles are also able to form hydrogels by forming physical interactions with each other to create a structure that locks in water. They also display the very unusual and potentially useful property of being extremely sticky for biological molecules. Over the past five years, EPSRC has funded my research exploring ways to use these properties for creating gel environments in the body that can activate stem cells to form bone. We have developed gels that can be injected into an injury site to deliver and bind bone growth factors and stimulate bone formation at much lower doses than previously reported. However, though promising, our approach of injecting large volumes of gel with protein mixed uniformly through is rather crude when compared with the precise concentration gradients that regulate bone formation in the body. Over the course of this exploration we have, however, discovered a new unexpected property of nanoclay gels that could potentially make them even more effective at stimulating regeneration. As well as being able to hold onto mixed-in growth factors, we have now found a simple way to precisely pattern the arrangement of these biomolecules within the gel itself. This is very exciting as it could allow us to begin to mimic the intricate patterning so important in natural stem cell behaviour. The current funding will allow us to explore this property and test ways to apply clay biomolecule patterning in regenerative medicine. It is exciting because we do not currently understand how and why these patterns form and so we are working with physicists specialising in nanoparticle gels to gain new insights into this surprising behaviour. It is also exciting because it allows a new approach to exploring the role of biomolecule patterning in stem cell repair and regeneration. We hope that this work will allow us to harness, more effectively and reliably, the great potential of stem cells to cure disease.