Abstract
ABSTRACTVascularization plays a significant role in treating nerve injury, especially to avoid the central necrosis observed in nerve grafts for large and long nerve defects. It is known that sufficient vascularization can sustain cell survival and maintain cell integration within tissue‐engineered constructs. Several studies have also shown that vascularization affects nerve regeneration. Motivated by these studies, vascularized nerve grafts have been developed using various different techniques, although donor site morbidity and limited nerve supply remain significant drawbacks. Tissue engineering provides an exciting alternative approach to prefabricate vascularized nerve constructs which could overcome the limitations of grafts. In this review article, we focus on the role of vascularization in nerve regeneration, discussing various approaches to generate vascularized nerve constructs and the contribution of tissue engineering and mathematical modeling to aid in developing vascularized engineered nerve constructs, illustrating these aspects with examples from our research experience. Anat Rec, 301:1657–1667, 2018. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.
Highlights
The vasculature plays a fundamental role in supporting the function of peripheral nerves through its supply of blood, oxygen and other nutrients to the cells comprising nerve tissue
The extrinsic system comprises a series of arteries and veins which run along the surface of a peripheral nerve and mainly supply the epineurial and perineurial regions (Fig. 1)
In a study undertaken in dogs, Tarlove and Epstein (1945) reported that the rate of vascularization seemed to limit the growth of axons into a peripheral nerve graft
Summary
The vasculature plays a fundamental role in supporting the function of peripheral nerves through its supply of blood, oxygen and other nutrients to the cells comprising nerve tissue. Vascular endothelial growth factor (VEGF) added in a silicone chamber was shown to significantly increase vascularization and enhance axonal regrowth and Schwann cell proliferation in a rat sciatic nerve injury model, indicating the interdependence between the vascularization and nerve regeneration processes (Hobson et al, 2000). Recent studies have shown that molecular cues from nerves influence the branching and network morphology of blood vessels and vice versa, suggesting cross-talk between neural cells and vascular cells. Exercise induced increased synaptic activity and a greater density of blood vessels in the cerebellar cortex of adult rats (Black et al, 1990) These studies provide further data to support the relationship between blood vessels and nerves, as well as suggesting that endothelial cells could help promote neurite elongation by providing molecular cues in the early stage of regeneration. Vascularized nerve constructs are reviewed, future technological directions including engineered tissues and mathematical modeling are discussed using examples from our current research
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