It is more than 50 years since J.T. Hueston, R.M. McFarlane, and others initiated new research programs focused on optimizing the treatment and understanding the pathogenesis of Dupuytren Disease (Hueston 1962; Luck 1959; McFarlane and Jamieson 1966). While we have seen the development of some new treatment alternatives, our understanding of the molecular pathogenesis of this fibrosis has remained at a rudimentary level. The central aim of basic Dupuytren Disease research is to gain a detailed mechanistic understanding of how complex genomics interact with unique aspects of the palmar fascia microenvironment to cause fibrotic disease development, progression, and recurrence. One way to achieve this aim is to create representative models of Dupuytren Disease development in the laboratory. Such models could be used to identify novel therapeutic targets and provide test beds for optimizing these interventions. To achieve these models, we will need researchers with cutting-edge skills. While diverse arrays of skills are likely to be required, experts in the following three areas may be essential.

Tissue engineers will be needed to develop representative and reproducible models of Dupuytren Disease in the laboratory. The poorly defined and complex genomic traits that predispose individuals to develop Dupuytren Disease are unlikely to be replicated in nonhuman animal models. For this reason, the concept of engineering palmar fascia-like tissues in the laboratory and populating them with human cells carrying these complex traits is an attractive option. These models will require careful engineering to replicate the normal and fibrotic palmar fascia environment as closely as possible. They will need to utilize three-dimensional culture substrates with biomechanical properties that are similar to normal or fibrotic palmar fascia. As the palmar fascia experiences physiological stresses during normal hand use, these models should also be designed to receive such periodic stresses. These culture substrates must be suitable for “conditioning” with the complex mixtures of proteins and other molecules found in the extracellular matrices of normal and fibrotic palmar fascia. Finally, and most importantly, these models will not only need to replicate palmar fascia pre- and post-disease development, they will also need to replicate disease development, i.e., the transition process from visibly unaffected to fibrotic palmar fascia. This might be achieved by providing pro-fibrotic stimuli to induce cellular structures that are analogous to nodules or contracture cords to develop in long-term cultures. For example, studies have linked the presence of inflammatory cytokines to nodule development (Verjee et al. 2013), and the prevalence of Dupuytren Disease is increased in patients with otherwise unrelated immune-mediated diseases (Patel et al. 2014). While the list of requirements for such models is daunting, they are nonetheless essential if we hope to achieve a representative and reproducible test bed for the development of new therapeutic interventions. Human tissue-engineered models have already begun replacing animal models for preclinical testing and drug discovery (Ranga et al. 2014; Gohl et al. 2014; Tevlin et al. 2015), and individuals with skills in developing these models could be invaluable for advancing Dupuytren Disease research.