Neurovascularization serves as the prerequisite and assurance for fostering neurogenesis after peripheral nerve injury (PNI), not only contributing to the reconstruction of the regenerative neurovascular niche but also providing a surface and directionality for Schwann cell (SC) cords migration and axons elongation. Despite the development of nerve tissue engineering techniques has drawn increasing attention to the intervention approach for repairing nerve defects, systematic generalization summary of the efficient intervention to expedite nerve angiogenesis is still scarce. This review delves into the mechanisms by which macrophages within the nerve defect trigger angiogenesis after PNI and elucidates how the newborn vessels support nerve regeneration, and then extracts three major categories of strategies for producing vascularized nerves in vitro and in vivo from them, encompassing (1) in vitro prevascularization, (2) in vivo prevascularization, and (3) stimulation of neurovascularization in situ. Furthermore, we emphasize that the lack of accuracy for structure and spatiotemporal regulation, as well as the operational inconvenience and delayed connection to the host’s nerve stumps, have stuck the existing neurovascularization technology in the preclinical stage. The successful design of a future prospective clinical vascularized nerve scaffold should be guided by a comprehensive consideration of these aspects.

Mandibular defects caused by injuries, tumors, and infections are common and can severely affect mandibular function and the patient’s appearance. However, mandible reconstruction with a mandibular bionic structure remains challenging. Inspired by the process of intramembranous ossification in mandibular development, a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced. Moreover, the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible. The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function. According to the results of in vivo experiments, the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics. The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone, indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development. Thus, hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction. Moreover, the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.