For years, scientists endeavour to recreate nature, attempting to solve problems or simplify day-to-day living. As futuristic visions and fiction fringe reality, innovative concepts are shaped and grasp practical application. A particularly challenging but striking concept is the creation of organs-on-chip, in a perfect synergy between complexity and miniaturization. This concept arose naturally from conventional 3D culture systems and the goal is not to replace the organs themselves, but to design chips so realistic that are able to replicate enough of the organ’s features and functions, so these chips can be used for consistent fundamental research or drug testing (1).
This project aims to present for the first time a fully and innovative, low cost, safe, disposable and self-sustainable multiwell-microplate cellulose-based microfluidic system to sustain a full thuickness 3D skin model. Given the enduring interest on skin models, research focused on the design of skin-on-chip systems has been growing. These systems are targeted to enable in vitro investigation of skin functions and interactions, to study normal physiology, model pathological environments and explore drug discovery and substances testing applications, in a simple, ready-to-use, yet realistic platform. Nowadays, diverse approaches to these systems have already been proposed. Has this technology evolves diverse technical challenges arise. A particular hindrance for the widespread use in research laboratories of the existing systems is related with the materials normally used for the design of microfluidics and assembly of these systems, namely polydimethylsiloxane (PDMS). Despite its numerous advantages, its high gas permeability, absorption of organic compounds and required specialized machinery/complex and techniques, render it not amenable for the herein envisaged applications, and hinder scaling up and mass production. On the other hand, factors like technical robustness and sample handling, processing, collection and analysis are challenges that call for innovation. Within this scenario, SkinChip team’s complementary expertise and mutual interests will synergize to develop a skin-on-a-chip system, aiming technical simplicity and effectiveness, based on low-cost widely available materials and technologies. In order to do this, SkinChip’s team will explore diverse origin celluloses, from paper (plant) to bacterial sources, to assemble the skin-on-a-chip system. Cellulosic films will be used as substrates for the design of microfluidic platforms, using the lab-on-paper technology (2), intended to mimic vascularization, with controlled flow, to introduce external stimuli, such as electrical or mechanical, and to support multicellular growth. Our deconstructed vision of this chip serves a multifactorial purpose, aiming the control of each part that make up the overall complex 3D system, including the dynamic control of physical, chemical and gaseous gradients, ensure mimetic vascularization, introduce favourable stimuli and co-culture of skin cells and appendices. On the other hand, the technological simplicity of design will allow portability, ease of processes, but also affordability, in such a way that the skin-on-chip can be used both by limited-resources laboratories and by state-of-art infrastructures. SkinChip project aims to address these issues by proposing a strategy broken down into 5 complementary tasks, assessing not only the production and modification of cellulose based substrates, cellulosic microfluidic platforms through lab-on-paper technology and skin engineered constructs, but also the assembly of the overall complex 3D system and its comprehensive characterization. In the end, SkinChip project and team is focused on tackling technological and (bio)engineering challenges, using unexpected natural materials and techniques to produce low-cost chips able to support the growth of a skin equivalent, which will serve as a model for fundamental and applied studies. In fact, expected groundbreaking outcomes from SkinChip’s actions are the use of cellulose to build microfluidic devices aimed to sustain a pectin-based 3D functional skin model, with applied favourable electrical/mechanical stimuli.
To address the challenges of this project, a multidisciplinary team will be united under the umbrella of SkinChip. UM partner, including the PI, offer their expertise on processing and characterization of natural origin materials, and will work with cellulose to render it with the desirable properties to be used for the build up of SkinChip’s systems. I3N team will synergise with UM to design and build the acellular component of the chips, including the microfluidic system. In order to do this, I3N offers consolidated knowledge on paper microfluidics with the advantage expertise on lab-on-paper technology. INEB team will introduce the necessary skills to build the full-thickness skin equivalent, as it is experienced in biomaterials and tissue regeneration, including skin.