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

Abstract

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.

Microfluidic and Lab-on-a-Chip Systems for Cutaneous Wound Healing Studies

“…The removal of the cell blocking structure after cell attachment creates a wound defect. Cell migration assays for the analysis of molecular processes in wound healing while using microdevices to analyze cell-cell interactions [38], skin inflammation models-on-chip [39] (including hydrogel cell migration assays [40]), and chemotaxis chips [41] cannot be regarded as wound healing assays per se and are not elaborated upon in more detail in the current review.…”

Engineered microenvironment for the study of myofibroblast mechanobiology

“…However, a majority of fibroblasts differentiated to myofibroblast without the presence of macrophages, suggesting the important role of soluble factor in this system. 70 Patient-derived, decellularized ECM is another important platform for the study of the microenvironmental impact on myofiborblasts. Isolated human microvascular pericytes cultured on decellularized idiopathic pulmonary fibrosis (IPF) lung matrices underwent myofibroblastic differentiation in response to direct contact with the fibrotic ECM components.…”

Microfluidic Skin‐on‐a‐Chip Models: Toward Biomimetic Artificial Skin

“…[ 106 ] Furthermore, wound models have seen improvements in mimicking the inflammation phase when vascularized. [ 122 ]…”

“…[106] Furthermore, wound models have seen improvements in mimicking the inflammation phase when vascularized. [122] The vascularized skin model clearly plays an important role in mimicking pathological skin conditions, such as fibrosis, that rely on the complex interplay of epithelial and endothelial cells. [106,123] Hence, vascularization is one of the key requirements for successful skin disease modeling.…”