Numerical Modelling of Keratinocyte Behaviour: A Comprehensive Review of Biochemical and Mechanical Frameworks.

Keratinocytes are the primary cells of the epidermis layer in our skin. They play a crucial role in maintaining skin health, responding to injuries, and counteracting disease progression. Understanding their behaviour is essential for advancing wound healing therapies, improving outcomes in regenerative medicine, and developing numerical models that accurately mimic skin deformation. To create physically representative models, it is essential to evaluate the nuanced ways in which keratinocytes deform, interact, and respond to mechanical and biochemical signals. This has prompted researchers to investigate various computational methods that capture these dynamics effectively. This review summarises the main mathematical and biomechanical modelling techniques (with particular focus on the literature published since 2010). It includes reaction-diffusion frameworks, finite element analysis, viscoelastic models, stochastic simulations, and agent-based approaches. We also highlight how machine learning is being integrated to accelerate model calibration, improve image-based analyses, and enhance predictive simulations. While these models have significantly improved our understanding of keratinocyte function, many approaches rely on idealised assumptions. These may be two-dimensional unicellular analysis, simplistic material properties, or uncoupled analyses between mechanical and biochemical factors. We discuss the need for multiscale, integrative modelling frameworks that bridge these computational and experimental approaches. A more holistic representation of keratinocyte behaviour could enhance the development of personalised therapies, improve disease modelling, and refine bioengineered skin substitutes for clinical applications.