3D Bioprinting of immunocompetent skin equivalents for wound healing project

慢性伤口是一个重大的全球性问题，导致患者发病率，给世界各地的卫生服务带来巨大的财政负担。慢性伤口的发生率目前正在上升，因为最易受影响的人群--老年人和糖尿病人--正在迅速扩大1。2018年，NHS每年用于伤口护理的费用估计为83亿GB 2，而在美国，用于伤口治疗的费用估计为250亿美元。大约40%-60%的慢性伤口无法在3个月内愈合，需要更先进的伤口疗法，如胶原蛋白敷料来调节过度炎症4。目前，这类疗法的开发依赖于2D/3D器官模型的使用，这些模型无法复制天然皮肤的复杂结构和功能组织，导致研究和临床结果不佳。动物模型，包括猪和小鼠，经常被用作简单的2D/3D细胞培养模型的替代/补充系统，但存在一些缺点：1)昂贵；2)有限的慢性创伤模型(猪)；3)与人类条件的生理相关性有限(小鼠)5.3D Biopprint以逐层的方式操作，允许细胞和材料精确地空间沉积成3D结构，从而为仿生组织等效物的开发打开了新的机会。在这里，我们的目标是结合我们在先进材料、生物制造和生物反应器方面的专业知识，开发出与生理相关的3D皮肤模型。成功的候选人将建立在现有模型的基础上，并建立新的策略来生成分层的、多细胞的(如成纤维细胞、角质形成细胞)和具有免疫活性的替代物，以询问支撑皮肤修复的病理生理机制。

Chronic wounds are a significant global problem, causing patient morbidity and a substantial financial burden on health services worldwide. The incidence of chronic wounds is currently rising because those populations most susceptible, the elderly and diabetic, are rapidly expanding1. In 2018, the annual NHS spend on wound care was estimated at £8.3 billion2, while in the U.S. an estimated US$25 billion is spent on their treatment3.Approximately 40-60% of chronic wounds do not heal within 3 months and require more advanced wound therapies such as collagen-based dressings to regulate excess inflammation4. Currently, the development of such therapies is reliant on the use of 2D/3D organotypic models that fail to replicate the complex structural and functional organization of native skin, leading to poor research and clinical outcomes. Animal models, including porcine and mice, are often used as an alternative/complementary system to simplistic 2D/3D cell culture models, but present several drawbacks: 1) expensive; 2) limited chronic wound models (porcine); 3) limited physiological relevance to human conditions (mice)5. Operating in a layer-by-layer fashion, 3D Bioprinting allows for the precise spatial deposition of cells and materials into 3D constructs, thus opening new opportunities for the development of biomimetic tissue equivalents. Here we aim to combine our expertise in advanced materials, biofabrication and bioreactors to develop a physiologically relevant 3D skin model. The successful candidate will build on existing models and establish new strategies for the generation of stratified, multicellular (e.g. fibroblasts, keratinocytes) and immunocompetent surrogates, to interrogate pathophysiological mechanisms underpinning skin repair.