Neural tissue-engineered prevascularization in vivo enhances peripheral neuroregeneration via rapid vascular inosculation

• Published in: Materials today bio 2023-08, Vol.21, p.100718-100718, Article 100718
• Main Authors: Wang, Hongkui, Zhang, Ping, Lu, Panjian, Cai, Xiaodong, Wang, Gang, Xu, Xi, Liu, Ying, Huang, Tianyi, Li, Meiyuan, Qian, Tianmei, Zhu, Hui, Xue, Chengbin
• Format: Article
• Language: English
• Subjects: Full Length; Neuroregeneration; Peripheral nerve injury; Prevascularization; Tissue engineered nerve graft; Vascular inosculation
• ISSN: 2590-0064; 2590-0064
• DOI: 10.1016/j.mtbio.2023.100718

Neural tissue engineering techniques typically face a significant challenge, simulating complex natural vascular systems that hinder the clinical application of tissue-engineered nerve grafts (TENGs). Here, we report a subcutaneously pre-vascularized TENG consisting of a vascular endothelial growth factor-induced host vascular network, chitosan nerve conduit, and inserted silk fibroin fibers. Contrast agent perfusion, tissue clearing, microCT scan, and blood vessel 3D reconstruction were carried out continuously to prove whether the regenerated blood vessels were functional. Moreover, histological and electrophysiological evaluations were also applied to investigate the efficacy of repairing peripheral nerve defects with pre-vascularized TENG. Rapid vascular inosculation of TENG pre-vascularized blood vessels with the host vascular system was observed at 4 ​d bridging the 10 ​mm sciatic nerve defect in rats. Transplantation of pre-vascularized TENG in vivo suppressed proliferation of vascular endothelial cells (VECs) while promoting their migration within 14 ​d post bridging surgery. More importantly, the early vascularization of TENG drives axonal regrowth by facilitating bidirectional migration of Schwann cells (SCs) and the bands of Büngner formation. This pre-vascularized TENG increased remyelination, promoted recovery of electrophysiological function, and prevented atrophy of the target muscles when observed 12 weeks post neural transplantation. The neural tissue-engineered pre-vascularization technique provides a potential approach to discover an individualized TENG and explore the innovative neural regenerative process. Schematic illustration of an in vivo prevascularization of tissue-engineered nerve graft for the sciatic nerve repair. A subcutaneously pre-vascularized TENG consisting of a vascular endothelial growth factor (VEGF) induced host vascular network, chitosan nerve conduit, and inserted silk fibroin fibers. Rapid vascular inosculation occurred with the host vascular system to repair the 10 ​mm sciatic nerve defect in rat. [Display omitted] •An individualized TENG is developed for repairing sciatic nerve defect.•Rapid vascular inosculation via neural tissue-engineered prevascularization in vivo enhances peripheral neuroregeneration.•Pre-vascularization in vivo suppress proliferation and promote migration of vascular endothelial cell.•Early vascularization of TENG drive axonal regrowth by facilitating bidirectional migration of Schwann cel