Oral mucosa equivalents, prevascularization approaches, and potential applications

Background: Oral mucosa equivalents (OMEs) have been used as in vitro models (eg, for studies of human oral mucosa biology and pathology, toxicological and pharmacological tests of oral care products), and clinically to treat oral defects. However, the human oral mucosa is a highly vascularized tissue and implantation of large OMEs can fail due to a lack of vascularization. To develop equivalents that better resemble the human oral mucosa and increase the success of implantation to repair large-sized defects, efforts have been made to prevascularize these constructs. Purpose: The aim of this narrative review is to provide an overview of the human oral mucosa structure, common approaches for its reconstruction, and the development of OMEs, their prevascularization, and in vitro and clinical potential applications. Study selection: Articles on non-prevascularized and prevascularized OMEs were included, since the development and applications of non-prevascularized OMEs are a foundation for the design, fabrication, and optimization of prevascularized OMEs. Conclusions: Several studies have reported the development and in vitro and clinical applications of OMEs and only a few were found on prevascularized OMEs using different approaches of fabrication and incorporation of endothelial cells, indicating a lack of standardized protocols to obtain these equivalents. However, these studies have shown the feasibility of prevascularizing OMEs and their implantation in animal models resulted in enhanced integration and healing. Vascularization in tissue equivalents is still a challenge, and optimization of cell culture conditions, biomaterials, and fabrication techniques along with clinical studies is required.