Influencing Endothelial Cells' Roles in Inflammation and Wound Healing Through Nucleic Acid Delivery

Tissue engineering and wound-healing interventions are often designed for use in diseased and inflamed environments. In this space, endothelial cells (ECs) are crucial regulators of inflammation and healing, as they are the primary contact for recruitment of immune cells, as well as production of proinflammatory cytokines, which can stimulate or reduce inflammation. Alternatively, proliferation and spreading of ECs result in the formation of new vascular tissue or repair of damaged tissue, both critical for wound healing. Targeting ECs with specific nucleic acids could reduce unwanted inflammation or promote tissue regeneration as needed, which are two large issues involved in many regenerative medicine goals. Polymeric delivery systems are tools that can control the delivery of nucleic acids and prolong their effects. This review describes the use of polymeric vehicles for the delivery of nucleic acids to ECs for tissue engineering. Impact statement Tissue engineering is a rapidly growing field that has the potential to resolve many disease states and improve the quality of life of patients. In some applications, tissue-engineered strategies or constructs are developed to rebuild spaces damaged by disease or degeneration. To rebuild the native tissue, these constructs may need to interact with unwanted immune activity and cells. Various immune cells are often the focus of therapies as they are critical players in the inflammatory response; however, endothelial cells are also an extremely important and promising target in these cases. In addition, controlled delivery of specific-acting molecules, such as nucleic acids, is of growing interest for the regeneration and health of a variety of different tissues. It is important to understand what has been done and the potential of these targets and therapeutics for future investigation and advancements in tissue engineering.