Design and manufacture of an antimicrobial multi-layered scaffold for skin regeneration

厚薄皮肤损伤影响数百万人的生活质量；它们涉及大量组织的损失，通常与严重感染、烧伤或皮肤癌手术有关。黄金标准治疗是使用皮肤移植（通常从患者身体的另一个部位取出一块皮肤，然后附着在患处）。自体皮肤移植并不总是可用的，需要使用组织工程移植。组织工程方法在临床上是有用的，但它们也有局限性。目前的结构不能在皮肤细胞群正常存在于活体的生理条件下传递细胞；因此，有必要提供一种新的生物材料装置，这种装置可以复制细胞在天然皮肤中存在的物理空间。在这里，我们建议通过结合增材制造技术（如微立体光刻）的精度，PolyHIPE材料提供的孔隙度以及静电纺丝的临床相关性和工业规模，来创建多功能分层膜。在这个项目中工作的学生将探索创造一个智能设备，它将在一定程度上模仿天然皮肤的结构。该结构将结合3个单独的功能支架，其中包含(i)在真皮上皮连接处具有类似皮肤网状嵴的明确地形的多孔层（已显示出改善抗剪切性，增强营养物质扩散并有助于角质细胞分化）；这一层还将加入抗菌剂（包括铈和芦荟衍生物以及小糖分子）；（ii）电纺纳米纤维伪基底膜，以增强角质细胞的附着；（iii）多孔的下层，配备人工血管系统，以确保血液供应。

thickness skin injuries affect the quality of life of millions of people; they involve the loss of a big amount of tissue and they are normally associated with severe infections, burns or skin cancer surgery. The gold standard treatment is the use of a skin graft (a patch of skin that is normally removed from another area of the patient's body and then attached to the affected area). Autologous skin grafts are not always available and the use of tissue engineered grafts is needed. Tissue engineering approaches are clinically useful but they also have limitations. Current constructs do not deliver cells under the physiological conditions under which skin cell populations normally exist in the living body; therefore, there is a need for delivering new biomaterial devices that reproduce closely the physical space in which cells exist in the native skin.Here we propose to create a multifunctional hierarchical membrane by combining the precision of additive manufacturing techniques such as microstereolithography, the porosity offered by PolyHIPE materials and the clinical relevance and industrial scale up enabled by electrospinning. The student working on this project will explore the creation of a smart device which will mimic to a certain extent the structure of the native skin. The construct will combine 3 individual functional scaffolds containing (i) A porous layer with defined topography resembling the skin rete ridges at the dermal epithelial junction (which have shown to improve shear resistance, enhance nutrient diffusion and aid in keratinocyte differentiation); this layer will also incorporate antimicrobial agents (including cerium and Aloe Vera derivatives as well as small sugar molecules); (ii) an electrospun nanofibrous pseudo basement membrane to enhance keratinocyte attachment: (iii) a porous under layer equipped with artificial vasculature to ensure blood supply.