Suspended additive manufacturing of complex wounds for precision therapy testing

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.

Main questions to be answered:

1.  What are the cellular phenotypes that make up a complex wound and what is the composition of its matrix? This will be answered by sampling patient wounds and performing spatial transcriptomics on the samples to identify the cellular phenotype and spatial make-up of the wound
2. What cellular phenotypes and matrix components are common to most complex wounds. This will be answered by looking at numerous complex wound to generate a unifying “make up” of cells and matrix to be emulated through suspended additive manufacturing techniques.
3. Can we produce a “complex wound” model based on common components of the wounds using suspended additive manufacturing? This will be answered by multiple cell line suspended printing in hydrogels that have a simplified matrix and cellular profile to human complex wounds
4. Can wound therapies influence the complex wounds models? This will be answered by testing our partner therapies on this platform to see what the influence of cell based therapies such as lipogems will be on these complex wound surrogates.