Inflammation on a chip: from fabrication to electrically guiding immune fate

Patients with altered inflammatory response, due to metabolic diseases (e.g., diabetes mellitus), chronic inflammation, autoimmune diseases and pharmaceutical treatments often experience delayed or incomplete tissue repair, including poor bone healing [1]. Current therapeutic strategies rely on controlling stem cell differentiation and macrophage polarization towards pro-/anti-inflammatory cells, by using soluble factors and bio-instructive materials [2,3]. However, cells are also guided by biochemical cues. They respond to physical cues (e.g., mechanical [4] and vibration [5], bioelectricity [6,7]), regulating their fate and function. Therefore the use of biophysical cues has been increasingly investigated, at both laboratory and biobank scales for clinical applications and represents an emerging field in regenerative medicine, offering potentially safer, tunable and more precise approaches. 

In particular, the endogenous bioelectric signalling that is orchestrated by ion channels and ion pumps [7,8], referred to as the bioelectric code, has gained growing interest. Externally applied electric fields (EFs) can alter this code, influencing cell membrane potential, directing cell migration, and modulating cell function (e.g., stem cell differentiation, change in cytokine secretion in T-cells) [9–12]. Yet, there remains a critical knowledge gap on how EFs influence monocyte commitment towards pro-/anti-inflammatory macrophages. This lack of understanding slows down the point of translation to reach immune response regulation and tissue repair in clinical settings driven by electrical cues. 

To address this, the proposed PhD project will develop an “inflammation on a chip” device, designed to host, monitor and electrically guide monocytes to macrophage differentiation. This device will take advantage of a multidisciplinary approach, by integrating microelectrodes to deliver precise electrical stimulation protocols to drive monocytes to differentiate into macrophages, and a real time monitoring of inflammatory biomarkers to evaluate their commitment towards either pro- or anti-inflammatory cells within a microfluidic system integration. 

This innovative model will provide first insights into bioelectric regulation of inflammatory cells, opening new therapeutic avenues for tissue engineering, regenerative medicine and inflammation disorders. Beyond that, the inflammation on a chip device could become an essential model for studying immune cells in controlled microenvironments, opening the way to investigate patient specific responses, ultimately contributing to personalised medicine.