Reconstruction of eyelid defects, especially the posterior lamella, remains challenging because of its anatomical complexity, functional considerations, and aesthetic concerns. The goals of eyelid reconstruction include restoring eyelid structure and function and achieving an aesthetically acceptable appearance. An in-depth understanding of the complex eyelid anatomy and several reconstructive principles are mandatory to achieve these goals. Currently, there are multiple surgical treatment options for eyelid reconstruction, including different flaps, grafts, and combinations of them. This comprehensive review outlines the principles of reconstruction and discusses the indications, advantages, and disadvantages of currently available surgical techniques. We also propose our clinical thinking for solving specific clinical questions in eyelid reconstruction and offer perspectives on new potential methodologies in the future.

Epithelial tissue injury can occur on any surface site of the body, particularly in the skin or urethral mucosa tissue, due to trauma, infection, inflammation, and toxic compounds. Both internal and external body epithelial tissue injuries can significantly affect patients’ quality of life, increase healthcare spending, and increase the global economic burden. Transplantation of epithelial tissue grafts is an effective treatment strategy in clinical settings. Autologous bio-engineered epithelia are common clinical skin substitutes that have the specific advantages of avoiding tissue rejection, obviating ethical concerns, reducing the risk of infection, and decreasing scarring compared to donor grafts. However, epithelial cells are often obtained from the individual’s skin and mucosa through invasive methods, which cause further injury or damage. Urine-derived stem cells (USC) of kidney origin, obtained via non-invasive acquisition, possess high stemness properties, self-renewal ability, trophic effects, multipotent differentiation potential, and immunomodulatory ability. These cells show versatile potential for tissue regeneration, with extensive evidence supporting their use in the repair of epidermal and urothelial injuries. We discuss the collection, isolation, culture, characterization, and differentiation of USC. We also discuss the use of USC for cellular therapies as well as the administration of USC-derived paracrine factors for epidermal and urothelial tissue repair. Specifically, we will discuss 3D constructions involving multiple types of USC-loaded hydrogels and USC-seeded scaffolds for use in cosmetic production testing, drug development, and disease modeling. In conclusion, urine-derived stem cells are a readily accessible autologous stem cell source well-suited for developing personalized medical treatments in epithelial tissue regeneration and drug testing.

Reconstruction of posterior lamellar eyelids remains challenging due to their delicate structure, highly specialized function, and cosmetic concerns. Current clinically available techniques for posterior lamellar reconstruction mainly focus on reconstructing the contour of the eyelids. However, the posterior lamella not only provides structural support for the eyelid but also offers a smooth mucosal surface to facilitate globe movement and secrete lipids to maintain ocular surface homeostasis. Bioengineered posterior lamellar substitutes developed via acellular or cellular approaches have shown promise as alternatives to current therapies and encouraging outcomes in animal studies and clinical conditions. Here, we provide a brief reference on the current application of autografts, biomaterials, and tissue‐engineered substitutes for posterior lamellar eyelid reconstruction. We also shed light on future challenges and directions for eyelid regeneration strategies and offer perspectives on transitioning replacement strategies to regeneration strategies for eyelid reconstruction in the future.