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

皮肤是一个具有特殊功能层（感知，再生，保护）的活界面。皮肤的复杂程度目前在工程生物材料（ELM）中还没有达到。在这里，我们将创建皮肤启发的ELM与层与活细胞，专门的属性和功能。我们的活体皮肤是基于一个生长的基质，它承载着工程化的多细胞财团，这些财团构建并功能化了不同的层。时空模式是通过遗传控制和细胞和生物分子的物理化学性质来实现的。我们的目标是生成平台技术来推进生物ELMs，并制作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性治疗皮肤（LTS），由细菌纤维素水凝胶基质制成，具有感知和响应细胞。LTS将有一个具有传感功能的交互层，一个用于响应活细胞的核心层，以及一个用于生物防护和水合作用的屏障层。一个示例LTS将被设计为感测湿疹中的致病皮肤细菌并释放生物合成的治疗分子。将制造由生物矿化生物聚合物承载细菌孢子组成的干燥和坚韧的活再生皮肤（LRS），作为防护服中传统惰性材料（陶瓷，塑料）的替代品。LRS生物矿化核心将排列在微尺度层中，就像自然界中坚韧的生物矿物（珍珠层、骨、牙本质）。LRS将封装在活化剂外壳中，设计用于防止水渗透并记住局部机械经验，使机械应力区域局部自增强，与当前材料和其他ELM相比具有独特的性能。作为加速我们的生活材料在社会中的采用的有力战略，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，以使材料和产品开发协同发展。

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.