Much of R&D in skin health and disease has been centered on the use of 2D cultures and animal models. Recently, 3D skin models have provided platforms for toxicity testing, biomaterials evaluation, and investigation of fundamental biological processes. However, the majority these models lack an inflammatory system and other characteristics of native skin. Furthermore, the assays used to interrogate biological processes in these models are usually end point assays which require destruction of the skin model. Overall, this indicates scope for more physiologically complex and in situ monitored skin models. As a part of the Future Science Probing Biosystems program at CSIRO, we are developing an immune competent skin model that will be capable of evaluating a wide range of external challenges including bacterial infection. Using a multi-disciplinary capability in tissue engineering, biology and physics, the long term aim is to create a 3D skin model that is integrated with optical and chemical monitoring platforms which monitor in situ markers of infection and inflammation. Currently, we have developed a native like skin equivalent using telomerase reverse transcriptase (TERT)-immortalised keratinocytes and fibroblasts. Similar to that of native skin, these equivalents show native structural assembly and express early, intermediate and late differentiation markers in the epidermis, and a fibroblast marker in the dermis. Furthermore, we have developed a prototype microfluidic device that will be used to deliver media to provide a ‘flow’ of nutrients throughout the construct to assess whether this elongates culture life during bacterial infection. Future work will include the incorporation of immune cells into the skin model and concurrent biological characterization during infection and inflammation. Taking advantage of cellular processes and engineering requirements during the construction of new and more relevant models will allow smart ways of integrating in situ sensors into future skin models.