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

厚皮损伤影响数百万人的生活质量;它们涉及大量组织的损失，并且它们通常与严重感染、烧伤或皮肤癌手术有关。金标准治疗是使用皮肤移植（通常从患者身体的另一个区域去除一块皮肤，然后贴在受影响的区域）。自体皮肤移植并不总是可用的，需要使用组织工程移植物。组织工程方法在临床上是有用的，但它们也有局限性。目前的构建体不能在皮肤细胞群通常存在于活体中的生理条件下递送细胞;因此，需要提供新的生物材料装置，其紧密地再现细胞存在于天然皮肤中的物理空间。在此，我们提出通过结合增材制造技术（例如微立体光刻，PolyHIPE材料提供的多孔性以及静电纺丝实现的临床相关性和工业规模扩大。从事该项目的学生将探索创建一个智能设备，该设备将在一定程度上模仿天然皮肤的结构。该结构将结合联合收割机3个单独的功能性支架，包括（i）具有类似真皮上皮连接处皮肤网脊的限定形貌的多孔层（其已显示出改善抗剪切性、增强营养物扩散并有助于角质形成细胞分化）;该层还将包含抗微生物剂（包括铈和芦荟衍生物以及小的糖分子）;（ii）电纺纳米纤维假基底膜，以增强角质形成细胞附着：（iii）设有人造血管以确保血液供应的多孔底层。

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.