Abstract
Cutaneous wound healing is a complex, multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically, and biologically injured area, resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics are therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring, and eliminate chronic wounds. Following the global trend towards the automation, miniaturization, and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay and cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow for precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.
Highlights
Mechanical injuries, burns, and illnesses are, among others, the leading causes of external or internal tissue damage or lesion, generally referred to as wounds
Pathological conditions can interfere with the normal wound healing process and may lead to impaired or delayed wound healing such as diabetic ulcers and chronic wounds [3]
Conventional migration and wound healing assays based on cell exclusion or removal feature a range of limitations and are associated with endpoint detection, have non-linear or uncontrolled gradients, lack reproducibility, are not automation-friendly, require the manual removal of inserts, damage matrix coatings, and have variability between control and experiment scratching
Summary
Mechanical injuries, burns, and illnesses are, among others, the leading causes of external or internal tissue damage or lesion, generally referred to as wounds. Following wounding and blood flow restriction (clotting), the injured tissue undergoes three stages of regeneration—inflammation (localized swelling), new tissue formation (rebuilding), and maturation (remodeling), resulting in healed wound areas that are generally weaker than uninjured skin. These wound healing stages are complex and fragile, and it is well known that wound healing kinetics such as speed and efficiency vary in each individual depending on stress level, age, sex, and lifestyle [2]. To study tissue regeneration processes and screening treatment options, various in vitro wound healing assays have been established to elucidate the most influential factors and mechanisms that govern cell proliferation and migration. This review focuses on the current state of established microfluidic wound healing assays that assess the role of cell migration in the overall wound healing process including methods for wound generation, wound healing analysis schemes, and the influence of molecular stimuli and/or inhibitors (e.g., oxygen, serum content, growth factors, and small molecules) in mechanistic studies on cell migration and wound healing
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