3D Bioprinting of immunocompetent skin equivalents for wound healing project

慢性伤口是一个重要的全球性问题，导致患者发病率和世界各地的卫生服务的巨大财政负担。慢性伤口的发病率目前正在上升，因为最易感的人群，老年人和糖尿病患者，正在迅速扩大1。2018年，NHS在伤口护理上的年度支出估计为83亿英镑2，而在美国，估计有250亿美元用于治疗3。大约40-60%的慢性伤口在3个月内无法愈合，需要更先进的伤口治疗，如胶原蛋白敷料，以调节过度炎症4。目前，这种疗法的开发依赖于2D/3D器官型模型的使用，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，通常被用作简化的2D/3D细胞培养模型的替代/补充系统，但存在几个缺点：1）昂贵; 2）有限的慢性伤口模型（猪）; 3）与人类状况的生理相关性有限（小鼠）。3D生物打印以逐层的方式操作，允许细胞和材料精确地空间沉积到3D结构中，从而为仿生组织等同物的开发开辟了新的机会。我们的目标是联合收割机结合我们在先进材料、生物织物和生物反应器方面的专业知识，开发出一种生理相关的3D皮肤模型。成功的候选人将建立在现有的模型，并建立新的策略，分层，多细胞（如成纤维细胞，角质形成细胞）和免疫活性的替代品的产生，以询问病理生理机制支撑皮肤修复。

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.