Suspended additive manufacturing of complex wounds for precision therapy testing

复杂的伤口(腿部和压疮、创伤和烧伤)是常见的、高发病率和昂贵的问题。在英国，每1000人中有1.6人在任何时候都会受到复杂创伤的影响，估计每年的卫生服务费用超过50亿GB。到2020/21年度，大曼彻斯特复杂伤口的总体管理预计将达到3亿GB。反复就诊、换衣服带来的不适以及疾病的耻辱带来的心理负担是巨大的，这使这成为主要的医疗保健优先事项。这是一个在转化医学方面记录不佳的领域，满足医疗需求的证据治疗有限。科学界缺乏包含这些异质伤口复杂性的相关临床前模型。3D Biopprint提供了一条潜在的途径来生成3D组织模型，该模型能够通过精确地在多种材料、细胞和生物活性化合物的空间沉积来模拟天然伤口组织结构和功能的异质性。然而，大多数生物打印技术不允许在生理条件下直接制造构件。使用一种新的悬浮制造系统，可加载细胞的材料可以直接打印在充当支架系统的流体凝胶中，同时辅以细胞培养介质。使用患者复杂的伤口样本来绘制细胞异质性图，可以对与高级临床护理相关的临床前实验和分析开发进行精确建模。

Complex wounds (leg and pressure ulcers, trauma wounds and burns) are common, high morbidity and costly problems. In the UK >1.6 per 1000 of the population are affected by complex wounds at any one time with an estimated annual cost to the health service of over £5 billion. The overall management of complex wounds in Greater Manchester is projected to be £300 million by 2020/21. The psychological burden of repeated healthcare visits, discomfort of dressing changes, and stigmatisation of illness is significant, making this a major healthcare priority. This is an area with a poor track record in translational medicine, and limited evidenced therapies to meet healthcare needs. The scientific field lacks relevant preclinical models encompassing the complexity of these heterogeneous wounds. 3D Bioprinting offers a potential route to generate 3D tissue models capable of mimicking the native wound tissue structural and functional heterogeneity by the precise spatial deposition of multiple materials, cells and bioactive compounds. However, most of the bioprinting techniques do not allow for direct manufacturing of constructs under physiological conditions. Using a novel suspended manufacturing system, cell-loadable materials can be printed directly inside fluid gels which act as scaffolding systems whilst being supplemented with cell culture media. Using patient complex wound samples to map the cellular heterogeneity allows for precision modelling of preclinical experiments and assay development relevant to advance clinical care.