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This article provides a comprehensive overview of techniques and graft materials used for repairing peripheral nerve defects. It discusses current approaches to peripheral nerve injury, including autografts, allografts, and nerve conduits, and examines the advantages and disadvantages of each method. The authors emphasize the importance of considering both the material and topography of nerve conduits in promoting nerve regeneration. Different designs, such as conduits with porous walls, grooved walls, multichannels, and fillers, are explored. The article suggests that a combination of synthetic and natural polymers may be the ideal choice for nerve conduit fabrication. The text also highlights the significance of providing topographic cues in the design of conduits for repairing peripheral nerve defects, and offers strategies such as porous and grooved walls, multi-channel conduits, and the use of fillers like fibers or hydrogels to enhance the structure and bioactivation of conduits. The article includes author contributions, funding sources, conflict of interest, and a disclaimer that the claims expressed in the article are solely those of the authors. It also provides several references for further reading on the topic of nerve conduit design and peripheral nerve regeneration. [Extracted from the article]

In peripheral nerve injuries (PNI) with substance loss, where tensionless end-to-end suture is not achievable, the positioning of a graft is required. Available options include autografts (e.g., sural nerve, medial and lateral antebrachial cutaneous nerves, superficial branch of the radial nerve), allografts (Avance®; human origin), and hollow nerve conduits. There are eleven commercial hollow conduits approved for clinical, and they consist of devices made of a non-biodegradable synthetic polymer (polyvinyl alcohol), biodegradable synthetic polymers (poly(DL-lactide-ε-caprolactone); polyglycolic acid), and biodegradable natural polymers (collagen type I with/without glycosaminoglycan; chitosan; porcine small intestinal submucosa); different resorption times are available for resorbable guides, ranging from three months to four years. Unfortunately, anatomical/functional nerve regeneration requirements are not satisfied by any of the possible alternatives; to date, focusing on wall and/or inner lumen organization/functionalization seems to be the most promising strategy for next-generation device fabrication. Porous or grooved walls as well as multichannel lumens and luminal fillers are the most intriguing options, eventually also including the addition of cells (Schwann cells, bone marrow-derived, and adipose tissue derived stem cells) to support nerve regeneration. This review aims to describe common alternatives for severe PNI recovery with a highlight of future conduits. [ABSTRACT FROM AUTHOR]

Oxidized polyvinyl alcohol (OxPVA) is a new polymer for the fabrication of nerve conduits (NCs). Looking for OxPVA device optimization and coupling it with a natural sheath may boost bioactivity. Thus, OxPVA/chitosan sponges (ChS) as hybrid scaffolds were investigated to predict in the vivo behaviour of two-layered NCs. To encourage interaction with cells, ChS were functionalized with the self-assembling-peptide (SAP) EAK, without/with the laminin-derived sequences -IKVAV/-YIGSR. Thus, ChS and the hybrid scaffolds were characterized for mechanical properties, ultrastructure (Scanning Electron Microscopy, SEM), bioactivity, and biocompatibility. Regarding mechanical analysis, the peptide-free ChS showed the highest values of compressive modulus and maximum stress. However, among +EAK groups, ChS+EAK showed a significantly higher maximum stress than that found for ChS+EAK-IKVAV and ChS+EAK-YIGSR. Considering ultrastructure, microporous interconnections were tighter in both the OxPVA/ChS and +EAK groups than in the others; all the scaffolds induced SH-SY5Y cells' adhesion/proliferation, with significant differences from day 7 and a higher total cell number for OxPVA/ChS+EAK scaffolds, in accordance with SEM. The scaffolds elicited only a slight inflammation after 14 days of subcutaneous implantation in Balb/c mice, proving biocompatibility. ChS porosity, EAK 3D features and neuro-friendly attitude (shared with IKVAV/YIGSR motifs) may confer to OxPVA certain bioactivity, laying the basis for future appealing NCs. [ABSTRACT FROM AUTHOR]

The article focuses on nanocomposite conductive nerve conduits for peripheral nerve injury recovery, demonstrating the potential of these conduits, particularly those incorporating multiwalled carbon nanotubes (CNT), to enhance nerve regeneration and function in preclinical studies.

The surgical approach to peripheral nerve injuries (PNI) with substance loss depends on injury severity. If end-to-end suture is not possible, interposition of autologous nerve grafts represents the current gold standard [1]; however, growing interest is arousing towards effective comorbidities-free alternatives: nerve conduits (NCs). In this study, different NCs based on the new oxidized polyvinyl alcohol (OxPVA) [2,3] were implanted in a rat model of sciatic nerve transection (gap=5mm). Briefly, 18 animals were randomized to 6 groups implanted with: Reverse Autograft (RA, control); Reaxon® (commercial device made of chitosan); OxPVA; OxPVA+EAK peptide; OxPVA+EAK-YIGSR peptide; OxPVA+Nerve Growth Factor (NGF). The end point considered was 6 weeks. After implantation, both functional recovery assessment (i.e., gait analysis, sciatic functional index, von Frey filaments assay for mechanical sensitivity) and histological (hematoxylin and eosin, toluidine blue staining) and immunohistochemical (CD3, F4/80, S100, ß-tubulin) analyses occurred on explants. Eventual fibroconnective infiltrate was also evaluated by Second Harmonic Generation (SHG) microscopy. All the NCs sustained nerve regeneration as demonstrated by functional studies; OxPVA+NGF distinguished for better functional outcomes, like RA. Upon explant, all grafts were clearly recognizable without severe formation of fibrous tissue outside the NC; presence of n=1 neuroma was observed in Reaxon®. Histological/immunohistochemical analyses proved presence of regenerated nerve fibers in the central portion of all grafts (S100, ß-tubulin) in absence of lymphomonocytic infiltration (CD3, F4/80). In the centre of the NCs, morphometric analysis showed a total axons number that followed this descending order: OxPVA+EAK-YIGSR> RA>OxPVA>Reaxon®>OxPVA+NGF>OxPVA+EAK; in the distal portion, a decreasing total axon number was progressively displayed by: RA>OxPVA>OxPVA+EAK-YIGSR>OxPVA+ NGF>OxPVA+EAK>Reaxon®. SHG microscopy, revealed a less intense signal for: Reaxon®< OxPVA+EAK

The limitations and difficulties that nerve autografts create in normal nerve function recovery after injury is driving research towards using smart materials for next generation nerve conduits (NCs) setup. Here, the new polymer partially oxidized polyvinyl alcohol (OxPVA) was assayed to verify its future potential as a bioactivated platform for advanced/effective NCs. OxPVA-patterned scaffolds (obtained by a 3D-printed mold) with/without biochemical cues (peptide IKVAV covalently bound (OxPVA-IKVAV) or self-assembling peptide EAK (sequence: AEAEAKAKAEAEAKAK), mechanically incorporated (OxPVA+EAK) versus non-bioactivated scaffold (peptide-free OxPVA (PF-OxPVA) supports, OxPVA without IKVAV and OxPVA without EAK control scaffolds) were compared for their biological effect on neuronal SH-SY5Y cells. After cell seeding, adhesion/proliferation, mediated by (a) precise control over scaffolds surface ultrastructure; (b) functionalization efficacy guaranteed by bioactive cues (IKVAV/EAK), was investigated by MTT assay at 3, 7, 14 and 21 days. As shown by the results, the patterned groove alone stimulates colonization by cells; however, differences were observed when comparing the scaffold types over time. In the long period (21 days), patterned OxPVA+EAK scaffolds distinguished in bioactivity, assuring a significantly higher total cell amount than the other groups. Experimental evidence suggests patterned OxPVA-EAK potential for NCs device fabrication. [ABSTRACT FROM AUTHOR]

Functionalized synthetic conduits represent a promising strategy to enhance peripheral nerve regeneration by guiding axon growth while delivering therapeutic neurotrophic factors. In this work, hollow nerve conduits made of polyvinyl alcohol partially oxidized with bromine (OxPVA_Br2) and potassium permanganate (OxPVA_KMnO4) were investigated for their structural/biological properties and ability to absorb/release the ciliary neurotrophic factor (CNTF). Chemical oxidation enhanced water uptake capacity of the polymer, with maximum swelling index of 60.5% ± 2.5%, 71.3% ± 3.6% and 19.5% ± 4.0% for OxPVA_Br2, OxPVA_KMnO4 and PVA, respectively. Accordingly, hydrogel porosity increased from 15.27% ± 1.16% (PVA) to 62.71% ± 8.63% (OxPVA_Br2) or 77.50% ± 3.39% (OxPVA_KMnO4) after oxidation. Besides proving that oxidized PVA conduits exhibited mechanical resistance and a suture holding ability, they did not exert a cytotoxic effect on SH-SY5Y and Schwann cells and biodegraded over time when subjected to enzymatic digestion, functionalization with CNTF was performed. Interestingly, higher amounts of neurotrophic factor were detected in the lumen of OxPVA_Br2 (0.22 ± 0.029 µg) and OxPVA_KMnO4 (0.29 ± 0.033 µg) guides rather than PVA (0.11 ± 0.021 µg) tubular scaffolds. In conclusion, we defined a promising technology to obtain drug delivery conduits based on functionalizable oxidized PVA hydrogels. [ABSTRACT FROM AUTHOR]