Constrained by the existing scaffold inability to mimic limbal niche, limbal bio-engineered tissue constructed in vitro is challenging to be widely used in clinical practice. Here, a 3D nanofiber-aerogel scaffold is fabricated by employing thermal cross-linking electrospinned film polycaprolactone (PCL) and gelatin (GEL) as the precursor. Benefiting from the cross-linked (160 degrees C, vacuum) structure, the homogenized and lyophilized 3D nanofiber-aerogel scaffold with preferable mechanical strength is capable of refraining the volume collapse in humid vitro. Intriguingly, compared with traditional electrospinning scaffolds, the authors' 3D nanofiber-aerogel scaffolds possess enhanced water absorption (1100-1300%), controllable aperture (50-100 mu m), and excellent biocompatibility (optical density value, 0.953 +/- 0.021). The well-matched aperture and nanostructure of the scaffolds with cells enable the construction of limbal bio-engineered tissue. It is foreseen that the proposed general method can be extended to various aerogels, providing new opportunities for the development of novel limbal bio-engineered tissue.