Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound‐on‐a‐Chip Model

• Published in: Advanced healthcare materials 2019-01, Vol.8 (1), p.e1801307-n/a
• Main Authors: Biglari, Sahar, Le, Thi Y. L., Tan, Richard P., Wise, Steven G., Zambon, Alessandro, Codolo, Gaia, De Bernard, Marina, Warkiani, Majid, Schindeler, Aaron, Naficy, Sina, Valtchev, Peter, Khademhosseini, Ali, Dehghani, Fariba
• Format: Article
• Language: English
• Subjects: Adhesion tests; Cell culture; Cell Culture Techniques; Cell Differentiation - drug effects; Cellular Microenvironment; Collagen; Complex systems; Computer simulation; Cytokines; Cytokines - metabolism; Dermis - pathology; Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; drug screening; Endothelial cells; Fibroblasts; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Inflammation; Inflammation - drug therapy; Inflammation - pathology; Inflammation Mediators - metabolism; Lab-On-A-Chip Devices; Macrophages; Macrophages - drug effects; Microfluidics; Models, Biological; Myofibroblasts - drug effects; Myofibroblasts - pathology; Neovascularization, Physiologic - drug effects; organ‐on‐chips; Paracrine signalling; Skin; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Umbilical vein; Wound Healing
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.201801307

Considerable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost‐effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs). The wound‐on‐chip model consists of three interconnecting channels and is able to simulate wound inflammation by adding tumor necrosis factor alpha (TNF‐α) or by triculturing with macrophages. Both the approaches significantly increase IL‐1β, IL‐6, IL‐8 in the supernatant (p < 0.05), and increases in cytokine levels are attenuated by cotreatment with an anti‐inflammatory agent, Dexamethasone. Incorporation of M1 and M2 macrophages cocultured with fibroblasts and HUVECs leads to a stimulation of cytokine production as well as vascular structure formation, particularly with M2 macrophages. In summary, this wound‐on‐chip system can be used to model the paracrine component of the early inflammatory phase of wound healing and has the potential for the screening of anti‐inflammatory compounds. A 3D wound‐on‐a‐chip model is developed for coculturing human dermal fibroblasts and endothelial cells into the interconnected channels of a microfluidic device. The inflammation is simulated either by adding tumor necrosis factor alpha (TNF‐α) or having macrophages as immune cells. This microfluidic device is successfully used for screening the active compounds and assessing their anti‐inflammatory effects.