Living Therapeutic and Regenerative Materials with Specialised Advanced Layers (NextSkins)

皮肤是一个具有多层特殊功能（感知、再生、保护）的活界面。皮肤的复杂程度是目前工程生物材料（elm）所无法达到的。在这里，我们将创建具有活细胞层的皮肤灵感elm，具有专门的属性和功能。我们的活皮肤是建立在一个生长的基质上的，它承载着工程设计的多细胞联合体，可以构建不同的层并使其发挥功能。时空模式是通过遗传控制和细胞和生物分子的物理化学特性来实现的。我们的目标是产生平台技术来推进生物elm，并制造两种具有不同应用的概念验证工程活皮肤：我们将制造一种自封装的活治疗皮肤（LTS），由细菌纤维素水凝胶基质制成，具有感知和反应细胞。LTS将有一个具有传感功能的交互层，一个用于反应活细胞的核心层，以及一个用于生物控制和水合作用的屏障层。LTS将被设计用于检测湿疹中的致病性皮肤细菌，并释放生物合成的治疗分子。一种由承载细菌孢子的生物矿化生物聚合物组成的干燥坚韧的活再生皮肤（LRS）将被制造出来，作为传统惰性材料（陶瓷、塑料）的替代品。LRS生物矿化的岩心将排列成微尺度层，就像自然界中坚硬的生物矿物（珍珠层、骨、牙本质）一样。LRS将封装在活化剂外壳中，设计用于防止水渗透并记忆局部机械经验，使机械应力区域局部自我增强，与当前材料和其他elm相比，这是一种独特的特性。作为一项有力的战略，我们将系统地让潜在的最终用户和设计师参与我们的研究，以实现材料和产品开发的协同作用。

Skin is a living interface with layers of specialised functions (sensing, regeneration, protection). The level of complexity in skins is currently unreached in engineered living materials (ELMs). Here we will create skin-inspired ELMs with layers with living cells, specialised properties and functions. Our living skins are based on a grown matrix hosting engineered multicellular consortia that build and functionalise different layers. Spatiotemporal patterning is realised by genetic control and the physicochemical properties of cells and biomolecules. Our aim is to generate platform technologies to advance biological ELMs and make two proof-of-concept engineered living skins with different applications: We will fabricate a self-encapsulated Living Therapeutic Skin (LTS) made of a bacterial cellulose hydrogel matrix with sense-and-respond cells. LTS will have an interactive layer with sensing functions, a core layer for responsive living cells, and a barrier layer for biocontainment and hydration. An example LTS will be designed to sense pathogenic skin bacteria in eczema and release biosynthesised therapeutic molecules. A dry and tough Living Regenerative Skin (LRS) consisting of biomineralized biopolymers hosting bacterial spores will be fabricated as an alternative to traditional inert materials (ceramics, plastics) in protective garments. The LRS biomineralized core will arrange in microscale layers, like tough biominerals in nature (nacre, bone, dentin). LRS will be encapsulated in an activator shell, engineered to prevent water penetration and to memorize local mechanical experience, giving local self-reinforcement of mechanically stressed regions, a unique property compared to current materials and other ELMs. As a powerful strategy to accelerate the adoption of our living materials in society, we will systematically involve the potential end-users and designers in our research for the materials and product development to happen in synergy.