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Background/aim:
The aim of this study was to compare electrospun caprolactone (EC) and poly(lactic acid-ε-caprolactone) (PLCL) nerve conduits with nerve graft in a rat sciatic nerve defect model.
Materials and methods:
A total of 32 male Wistar albino rats were divided into 4 groups, with 8 rats in each group. A nerve defect of 1 cm was construc...
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Topographical cues on material surfaces are crucial for guiding the behavior of nerve cells and facilitating the repair of peripheral nerve defects. Previously, micron-grooved surfaces have shown great potential in controlling nerve cell alignment for studying the behavior and functions of those cells and peripheral nerve regeneration. However, the...
Citations
... In vivo studies further proved that the PLCL conduit could fully restore motor function (evaluated by triceps surae muscles weight ratio) and nerve conduction function (electrophysiological analysis) in 12 weeks, and the therapeutic effect was equal to that of the gold-standard treatment (autologous transplantation) [93]. Moreover, compared with the electrospun caprolactone group, PLCL conduit had a lower risk of neuroma formation or infection [94]. However, PLCL is highly hydrophobic and lacks cell recognition sites, and thus causes low biocompatibility [95]. ...
Peripheral nerve injuries resulting from various traumatic events can cause mobility problems and sensory impairment, jeopardizing patients’ life quality and bringing serious economic burdens. Due to the shortcomings of autologous nerve grafts, such as limited tissue sources, unmatched size, and loss of innervation at the donor site, tissue-engineered nerve grafts using both natural and synthetic materials have been employed in the treatment of peripheral nerve defect and to promote nerve regeneration. Apart from traditional advantages such as good biocompatibility and controllable degradation, the development of fabrication technology and the advancement in material science have endowed tissue-engineered nerve conduits with upgraded properties such as biomimetic surface topography, extracellular matrix components, neurotrophic factors, and cell seeding, or a conduit with micropores on the surface for substance exchange and/or with fillers inside for microenvironment simulation. This article reviews recent progress in the biomaterials employed in fabricating tissue-engineered nerve conduits, in vitro characterization, and their applications in nerve repair in animal studies as well as in clinical trials.
... However, there are a few recent studies investigating P(LLA-CL) itself or similar derivates in PNI. They proved effective in improving nerve regeneration of the nerve gap [35,36] or nerve coaptation site wrapping [37]. ...
The aim was to examine the efficiency of a scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen (COL), polyaniline (PANI), and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model. P(LLA-CL)-COL-PANI scaffold was optimized and electrospun into a tubular-shaped structure. Adipose tissue from 10 Lewis rats was harvested for ASCs culture. A total of 28 inbred male Lewis rats underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In Group A, the nerve gap remained untouched; in Group B, an excised trunk was used as an autograft; in Group C, nerve stumps were secured with P(LLA-CL)-COL-PANI conduit; in Group D, P(LLA-CL)-COL-PANI conduit was enriched with ASCs. After 6 months of observation, rats were sacrificed. Gastrocnemius muscles and sciatic nerves were harvested for weight, histology analysis, and nerve fiber count analyses. Group A showed advanced atrophy of the muscle, and each intervention (B, C, D) prevented muscle mass decrease (p < 0.0001); however, ASCs addition decreased efficiency vs. autograft (p < 0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the groups with the use of conduit (D vs. B p < 0.0001, C vs. B p < 0.001). P(LLA-CL)-COL-PANI conduits with ASCs showed promising results in managing nerve gap by decreasing muscle atrophy.
... However, there are a few recent studies investigating P(LLA-CL) itself or similar derivates in PNI. They proved effective in improving nerve regeneration of a nerve gap [26,27] or nerve coaptation site wrapping [28]. PCL is also combined with other particles, that may facilitate nerve regeneration, such as laminin [29] graphene [30], carbon nanotubes [31], small porcine intestine submucosa [32]. ...
Background: Peripheral nerve injuries (PNI) are trauma with severe squeals for patients’ quality of life. Currently, the gold standard of nerve reconstruction relies on primary coaptation. However, in case of a nerve gap, a reconstructive material for bridging is needed. Nerve conduits are an increasingly popular solution alternative to autografts or processed nerved allografts. The aim of the study was to examine the efficiency of a novel bioactive nanofiber-based tubular scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen, polyaniline and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model.
Methods: Poly (L-lactic acid)-co-poly(ϵ-caprolactone) scaffold was optimized and enriched with collagen (COL) and polyaniline (PANI) to create final (P(LLA-CL)-COL-PANI), tubular-shaped scaffold, manufactured with electrospinning technology. Parallelly, adipose tissue from 10 Lewis rats was harvested for ASC culture. 28 inbred male Lewis rats were divided into four even groups. Each animal underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In group A, nerve gap remained untouched, in B excised trunk was rotated and used as an autograft, in C nerve stumps were secured with P(LLA-CL)-COL-PANI conduit. In the D group gap was reconstructed with P(LLA-CL)-COL-PANI conduit enriched with ASCs. After 6-months of observation rats were sacrificed. Gastrocnemius muscles (operated and non-operated side) and reconstructed sciatic nerves were harvested for analyses. Muscles were weighted and underwent histological analysis. Nerves were processed and stained immunohistochemically with NF-200 to be analyzed with dedicated software for nerve fiber count.
Results: No signs of rejection or excessive fibrosis was noted. Muscle mass ratio was highest in group B (0.77±0.05), then in C (0.74±0,04) and D (0.67± 0.07). Group A showed advanced atrophy of the muscle, each intervention prevented muscle mass decrease (p<0.0001), however, ASC addition decreased efficiency vs autograft (p<0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the group with the use of conduit vs autograft (D vs B p<0.0001, C vs B p<0.001). ASC added to the conduit decreased perineurium hyperplasia.
Conclusion:
P(LLA-CL)-COL-PANI conduits with ASC showed promising results in managing nerve gap by decreasing muscle atrophy and providing a favorable environment for peripheral nerve regeneration.
In this study, we investigated the application of poly (lactic acid-co-glycolic acid) in the rat Achilles tendon injury model for the prevention or alleviation of peritendinous adhesion and guidance of Achilles tendon regeneration. In the study, 48 rats were used and the rats were randomized by closed envelope method and divided into 4 mating groups in groups of 12. Left Achilles tendons of the non-PLGA-treated control group (groups 1 and 2) were cut and repaired. In the PLGA-treated groups (groups 3 and 4) the left Achilles tendons were cut and repaired, then PLGA bioabsorbable material was wrapped around the repair line. The rats in the 1st and 3rd groups were sacrificed at the end of the 1st month, and the rats in the 2nd and 4th groups at the end of the 2nd month.
The degree of tendon adhesion in the Group 3 was lower in comparison with Group 1. Similarly, compared with Group 2, the degree of tendon adhesion in the Group 4 was lower. Inflammatory density, vascularization and fibrosis were higher in the experimental group. When the Group 3 and Group 1, and Group 2 and Group 4 were compared, adhesion length (p=0.004, p=0.041), adhesion characteristics (p=0.049, p=0.039) and adhesion severity (p=0.007, p=0.025) were found have statistically significant tendon healing in the PLGA-treated group, respectively. Significant difference was observed in inflammatory cell density, vascular density and fibrosis for Group 1 and Group 3, (p=0.027, p=0.041, p=0.002), respectively. Similarly, significant difference was observed in inflammatory cell density, vascular density and fibrosis for Group 2 and Group 4, (p=0.002, p=0.027, p=0.011), respectively.
As a result, it was considered that poly (lactic acid-co-glycolic acid) material significantly reduces peritendinous adhesions, and this effect could occur with the vascular density, inflammatory density and fibrosis as indicated in histopathological examination. These data suggest that PLGA membrane has good biocompatibility and alleviates tendon adhesion after injury.
Nerve conduits could be used to provide a bridge between both nerve endings. In this study, the tuba uterina of female rats were prepared in a vascularized pedicled flap model and it used as a nerve conduit. The aim was to investigate the effectiveness of a vascularized pedicle nerve conduit and its ciliated epithelium in a sciatic nerve defect. The study was conducted between May and August 2018, and used a total of 60, 14–16-week-old female Wistar albino rats. Six groups were created; Cut and Unrepaired Group, Nerve Graft Group, Flap-Forward Group (Tuba uterina tubular flap, forward direction), Flap-Reversed Group (Tuba uterina tubular flap, reverse direction), Graft-Forward Group (Tuba uterina tubular graft, forward direction) and Graft-Reverse Group (Tuba uterina tubuler graft, reverse direction). Nerve regeneration was evaluated 3 months (90 days) after the surgery by the following methods: (1) Sciatic Functional Index (SFI) measurement, (2) Electromyographic (EMG) assessment, (3) Microscopic assessment with the light microscope and (4) Microscopic assessment with the electron microscope. According to the SFI, EMG and microscopic assessments with the light and electron microscope, it was observed that the transfer of tuba uterina tubular conduit as a graft was statistically better in its effect on nerve regeneration than flap transfer, but also indicated that the direction of the ciliated structures had no significant effect. We believe that as this model is improved with future studies, it will shed light on new models, ideas and innovations about nerve conduits.
The feasible fabrication of nerve guidance conduits (NGCs) with good biological performance is important for translation in clinics. In this study, poly(d,l‐lactide‐co‐caprolactone) (PLCL) films loaded with various amounts (wt; 5%, 15%, 25%) of methylcobalamin (MeCbl) are prepared, and are further rolled and sutured to obtain MeCbl‐loaded NGCs. The MeCbl can be released in a sustainable manner up to 21 days. The proliferation and elongation of Schwann cells, and the proliferation of Neuro2a cells are enhanced on these MeCbl‐loaded films. The MeCbl‐loaded NGCs are implanted into rats to induce the regeneration of 10 mm amputated sciatic nerve defects, showing the ability to facilitate the recovery of motor and sensory function, and to promote myelination in peripheral nerve regeneration. In particular, the 15% MeCbl‐loaded PLCL conduit exhibits the most satisfactory recovery of sciatic nerves in rats with the largest diameter and thickest myelinated fibers. Methylcobalamin (MeCbl)‐loaded poly(d,l‐lactide‐co‐caprolactone) (PLCL) films can effectively promote the elongation and proliferation of Schwann cells, and the proliferation of Neuro2a cells in vitro, and MeCbl‐loaded PLCL conduits can effectively promote the regeneration of the amputated sciatic nerve of rats in vivo. In particular, the 15% MeCbl‐loaded PLCL conduit showed the best performance with the largest myelinated fibers and thickest myelin.
Peripheral nerve injury is a common disease that affects more than 20 million people in the United States alone and remains a major burden to society. The current gold standard treatment for critical-sized nerve defect is autologous nerve graft transplantation; however, this method is limited in many ways and does not lead to satisfactory outcomes. The limitations of autografts have prompted investigations into artificial neural scaffolds as replacements, and some neural scaffold devices have progressed to widespread clinical use, scaffold technology overall has yet to be shown to be consistently on par with or superior to autografts. Recent advances in biomimetic scaffold technologies have opened many new and exciting opportunities, and novel improvements in material, fabrication techniques, scaffold architecture, and lumen surface modifications that better reflect biological anatomy and physiology have all independently been shown to benefit overall nerve regeneration. Furthermore, biomimetic features of neural scaffolds have also been shown to work synergistically with other nerve regeneration therapy strategies such as growth factor supplementation, stem cell transplantation, and cell surface glycoengineering. This review summarizes the current state of neural scaffolds, highlights major advances in biomimetic technologies, and discuss future opportunities in the field of peripheral nerve regeneration.
