Suspended additive manufacturing of complex wounds for precision therapy testing

复杂伤口（腿部和压力性溃疡、创伤伤口和烧伤）是常见的、高发病率和昂贵的问题。在英国，每1000人中有>1.6人在任何时候受到复杂伤口的影响，估计每年的医疗服务费用超过50亿英镑。大曼彻斯特复杂伤口的整体管理预计到2020/21年度将达到3亿英镑。反复就诊、换药不适和疾病污名化的心理负担很大，使其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，并且满足医疗保健需求的证据疗法有限。科学领域缺乏涵盖这些异质性伤口复杂性的相关临床前模型。3D生物打印提供了一种潜在的途径来生成3D组织模型，该模型能够通过多种材料、细胞和生物活性化合物的精确空间沉积来模拟天然伤口组织的结构和功能异质性。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建体。使用一种新型的悬浮制造系统，细胞培养材料可以直接打印在流体凝胶内，流体凝胶作为支架系统，同时补充细胞培养基。使用患者复杂伤口样本来绘制细胞异质性允许临床前实验的精确建模和与先进临床护理相关的测定开发。

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.