Innervation in corneal bioengineering

Given the crucial role nerves play in maintaining corneal function and integrity, the ability of bioengineered cornea to demonstrate functional nerve regeneration directly influences their longevity and stability. Despite advances in biofabrication techniques and an increasing appreciation of the importance of neural innervation, to this day none have completely replicated the complexity and functionality of the cornea with successful innervation. This review evaluates the materials and fabrication techniques used to produce and enhance innervation in bioengineered cornea. Approaches to facilitating innervation are discussed and methods of assessing innervation compared. Finally, current challenges and future directions for innervated bioengineered cornea are presented, providing guidance for future work. STATEMENT OF SIGNIFICANCE: The functional nerve regeneration in bioengineered corneas directly influences their longevity and stability. Despite advancements in biofabrication techniques and growing recognition of the importance of neural innervation for bioengineered cornea, there remains a lack of comprehensive reviews on this topic. This review addresses the critical gap by evaluating the materials and fabrication techniques employed to promote innervation in bioengineered corneas. Additionally, we discuss various approaches to enhancing innervation, compare assessment methods, and examine both in vitro and in vivo responses. By providing a comprehensive overview of the current state of research and highlighting challenges and future directions, this review aims to provide guidance for inducing innervation of bioengineered cornea.