Abstract
The immune system has a crucial role in skin wound healing and the application of specific cell-laden immunomodulating biomaterials emerged as a possible treatment option to drive skin tissue regeneration. Cell-laden tissue-engineered skin substitutes have the ability to activate immune pathways, even in the absence of other immune-stimulating signals. In particular, mesenchymal stem cells with their immunomodulatory properties can create a specific immune microenvironment to reduce inflammation, scarring, and support skin regeneration. This review presents an overview of current wound care techniques including skin tissue engineering and biomaterials as a novel and promising approach. We highlight the plasticity and different roles of immune cells, in particular macrophages during various stages of skin wound healing. These aspects are pivotal to promote the regeneration of nonhealing wounds such as ulcers in diabetic patients. We believe that a better understanding of the intrinsic immunomodulatory features of stem cells in implantable skin substitutes will lead to new translational opportunities. This, in turn, will improve skin tissue engineering and regenerative medicine applications.
Highlights
We explored the use of human endothelial cells derived from freshly isolated adipose stromal vascular fraction (SVF) in a 3D coculture model of vascularized skin substitute in full-thickness wounds in immune-deficient rats [8]
Fibrin can bind vascular endothelial growth factor (VEGF)-C during the wound healing process, and this sequestration is necessary for lymphangiogenesis or the formation lymphatic vessels, which plays a key role in maintaining communication between antigen-presenting cells and the adaptive immune compartment [297]
Recent findings have greatly improved our understanding of the roles of the immune system in acute wound healing
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Human skin is composed of three layers, the epidermis, dermis, and hypodermis with complex cells, nerve, and blood supply [17,18]. Full-thickness wounds are injuries of the epidermis, dermis including the sweat glands and hair follicles, and the underlying subcutaneous fat or deeper tissues as well [25]. Chronic wounds are tissue injuries that heal slowly and often show delayed healing as 12 weeks from the injury. Different factors such as diabetes, malignancies and ongoing immunosuppressive treatment, poor primary wound treatment, and persistent infections of wounds can impair the healing process, leading to chronic nonhealing wounds [25]
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