Biocompatible Polyurethane Conduit Grafted with Vascular Endothelial Growth Factor‐Loaded Hydrogel Repairs the Peripheral Nerve Defect in Rats

Abstract

Artificial nerve guidance conduits (NGCs) can be potentially used to address the problems of peripheral nerve defects. The biomaterial polyurethane (PU) has already been used to construct NGCs. However, the use of a combination of PU-based NGCs and other bioactive cues, such as extracellular matrix proteins and growth factors, has not been reported yet. A PU conduit grafted with a vascular endothelial growth factor (VEGF)-loaded hydrogel (abbreviated as PU/Gel/VEGF conduit) is fabricated. The leachate generated during the use of the PU/Gel/VEGF conduit could facilitate the proliferation, migration, and expression of the neural marker S100𝜷 in RSC96 cells (in vitro). The walking track and target muscle are analyzed, and it is observed that PU/Gel/VEGF conduits promote the functional recovery of the injured side. Various histological staining analyses are carried out, and the results reveal that the PU/Gel/VEGF conduit effectively improves the extent of nerve regeneration achieved. The number of blood vessels developed during the regeneration of the axons in the PU/Gel/VEGF group (attributable to the pro-angiogenic effect of the functional NGC) is higher than the number of blood vessels developed in the PU/Gel conduit. Overall, the results indicate that PU/Gel/VEGF conduits could promote the process of peripheral nerve regeneration.

Composite Hydrogel Conduit Incorporated with Platelet-Rich Plasma Improved the Regenerative Microenvironment for Peripheral Nerve Repair

“…The regeneration of the injured nerve was further checked by triple fluorescence staining of neurofilament protein 200 (NF200) and Schwann cell marker protein 100 (S100). 53 As shown in Figure 6a, the densities of the nerve fibers within the GelMA/SA-3/PRP-20 and autograft group were significantly higher than that in GelMA/SA-3 group at 12 weeks after surgery. A large amount of NF200 and S100 positive staining cells were detected in GelMA/SA-3/PRP-20 and autograft groups, while few of them were detected in the GelMA/SA-3 group.…”

“…The regeneration of the injured nerve was further checked by triple fluorescence staining of neurofilament protein 200 (NF200) and Schwann cell marker protein 100 (S100) . As shown in Figure a, the densities of the nerve fibers within the GelMA/SA-3/PRP-20 and autograft group were significantly higher than that in GelMA/SA-3 group at 12 weeks after surgery.…”

Natural Polymer‐Derived Bioscaffolds for Peripheral Nerve Regeneration

“…[94] Xu et al injected VEGF-encapsulated GelMA hydrogel into hollow NGCs to achieve a similar effect (Figure 5A). [95] In addition, Xu and co-workers prepared injectable CS-HA hydrogels containing NGF to fill NGCs for NGF protection and sustained release (Figure 5B). [96] Bellamkon's group proposed agarose gel combined with lipid microtubules (hollow open tubules composed of one or more lipid bilayer membranes) to construct NGF gradient distribution anisotropic gels as conduit fillers.…”

“…Reproduced with permission. [95] Copyright 2021, Wiley-VCH. B) Schematic graph of injectable NGF-embedded HA/CS hydrogel filling.…”

“…It was proved to promote functional recovery of the injured side, as well as angiogenesis and nerve regeneration. [95] Although these fully filled hydrogels can adapt to complexshaped defects through minimally invasive implantation procedures, the difficulty of low cellular penetration for tissue regeneration must be considered. For this purpose, the AMH hydrogel filler presented by Hsu and co-workers provided mechanical support and biological cues for rapid cell migration, adhesion, and growth (Figure 8A).…”