Development of pro-angiogenic skin substitutes for wound healing

Wounds pose significant challenges to public health, primarily due to the loss of the mechanical integrity and barrier function of the skin and impaired angiogenesis, causing physical morbidities and psychological trauma to affect patients. Reconstructing the vasculature of the wound bed is crucial for promoting wound healing, reducing scar formation and enhancing the quality of life for patients. The development of pro-angiogenic skin substitutes has emerged as a promising strategy to facilitate vascularization and expedite the healing process of burn wounds. This review provides an overview of the various types of skin substitutes employed in wound healing, explicitly emphasising those designed to enhance angiogenesis. Synthetic scaffolds, biological matrices and tissue-engineered constructs incorporating stem cells and primary cells, cell-derived extracellular vesicles (EVs), pro-angiogenic growth factors and peptides, as well as gene therapy-based skin substitutes are thoroughly examined. The review summarises the existing challenges, future directions and potential innovations in pro-angiogenic dressing for skin substitutes. It highlights the need for continued research to develop new technologies and combine multiple strategies and factors, and to overcome obstacles and advance the field, ultimately leading to improved outcomes for wound patients.