The role of vascularization in nerve regeneration of nerve graft

Abstract

Vascularization is an important factor in nerve graft survival and function. The specific molecular regulations and patterns of angiogenesis following peripheral nerve injury are in a broad complex of pathways. This review aims to summarize current knowledge on the role of vascularization in nerve regeneration, including the key regulation molecules, and mechanisms and patterns of revascularization after nerve injury. Angiogenesis, the maturation of pre-existing vessels into new areas, is stimulated through angiogenic factors such as vascular endothelial growth factor and precedes the repair of damaged nerves. Vascular endothelial growth factor administration to nerves has demonstrated to increase revascularization after injury in basic science research. In the clinical setting, vascularized nerve grafts could be used in the reconstruction of large segmental peripheral nerve injuries. Vascularized nerve grafts are postulated to accelerate revascularization and enhance nerve regeneration by providing an optimal nutritional environment, especially in scarred beds, and decrease fibroblast infiltration. This could improve functional recovery after nerve grafting, however, conclusive evidence of the superiority of vascularized nerve grafts is lacking in human studies. A well-designed randomized controlled trial comparing vascularized nerve grafts to non-vascularized nerve grafts involving patients with similar injuries, nerve graft repair and follow-up times is necessary to demonstrate the efficacy of vascularized nerve grafts. Due to technical challenges, composite transfer of a nerve graft along with its adipose tissue has been proposed to provide a healthy tissue bed. Basic science research has shown that a vascularized fascial flap containing adipose tissue and a vascular bundle improves revascularization through excreted angiogenic factors, provided by the stem cells in the adipose tissue as well as by the blood supply and environmental support. While it was previously believed that revascularization occurred from both nerve ends, recent studies propose that revascularization occurs primarily from the proximal nerve coaptation. Fascial flaps or vascularized nerve grafts have limited applicability and future directions could lead towards off-the-shelf alternatives to autografting, such as biodegradable nerve scaffolds which include capillary-like networks to enable vascularization and avoid graft necrosis and ischemia.

Targeted Nipple Areola Complex Reinnervation: Technical Considerations and Surgical Efficiency in Implant-based Breast Reconstruction

“…Although a direct comparison between vascularized and nonvascularized nerve grafts is not available, there is evidence to suggest that vascularized pedicled and free nerve transfers are superior to nonvascularized grafts. 21,22 In addition, our technique is based on patient anatomy. In our experience it is easier to achieve a tensionless repair, maximum donor axon count, and donor nerve to allograft size match when the nerve reconstruction technique is individualized.…”

Surgical Angiogenesis of Decellularized Nerve Allografts Improves Early Functional Recovery in a Rat Sciatic Nerve Defect Model

“…10,50,51 Blood vessels have been found to precede neural regeneration and stimulate injured axons and nonneuronal cells to produce a supportive microenvironment after nerve injury. 35,52,53 Moreover, capillary changes and Schwann cell migration suggest axon growth, 54 explaining improved early functional recovery. Although surgical angiogenesis to the allograft continued increasing vascularity in the graft at 16 weeks, functional outcomes did not improve at this time point.…”

Large‐gap peripheral nerve repair using xenogeneic transplants in rhesus macaques

“…17 Therefore, vasculature that can be co-opted to restore perfusion would be advantageous. 18 Lastly, manufacturing ability, storage, and clinical acceptability are other critical considerations.…”

“…In addition, research indicates that return of perfusion is critical, as diffusion of oxygen, nutrients, and cytokines relies on a network of longitudinally arranged blood vessels that courses throughout the nerve 17 . Therefore, vasculature that can be co‐opted to restore perfusion would be advantageous 18 . Lastly, manufacturing ability, storage, and clinical acceptability are other critical considerations.…”