Bridging Gaps in Oral Mucosa Regeneration: Advances and Challenges

The repair and reconstruction of oral mucosal defects are critical for restoring both function and aesthetics of the oral cavity. Tissue engineering, which integrates principles from engineering and life sciences, has enabled the development of biological substitutes that closely mimic the native structure and function of oral mucosa, significantly reducing the risks and complications associated with autologous transplantation. With the rapid advancement of tissue-engineered oral mucosa (TEOM) technology, its applications in regenerative medicine and oral disease modeling have become increasingly prominent. In recent years, innovative strategies such as the development of organoids, prevascularization, immunomodulation, and dermal-epidermal junction biomimicry have emerged, providing effective solutions to challenges related to inadequate vascularization, immune dysregulation, and mechanical performance in TEOM constructs. In addition, the application of cutting-edge manufacturing technologies such as 3D bioprinting has accelerated the translation of TEOM toward clinical use. This review outlines the fundamental principles, design strategies, and potential applications of TEOM, and discusses novel approaches and challenges that must be addressed to facilitate its clinical implementation. Impact Statement This review provides a critical synthesis of recent advances in tissue-engineered oral mucosa, emphasizing cutting-edge methodologies in biomaterial development, cell engineering, and microenvironment modulation. By identifying unresolved challenges such as vascularization and immunomodulation, and proposing innovative strategies, including organoids and smart biomaterials, this article provides a valuable framework for researchers and clinicians striving to translate laboratory breakthroughs into effective regenerative therapies. This integrative perspective is poised to accelerate progress in oral mucosal repair across a variety of clinical applications.