Nerve Guidance Conduits Research Articles

Nanofibrous nerve guidance conduits decorated with decellularized matrix hydrogel facilitate peripheral nerve injury repair.

Rationale: Peripheral nerve injury (PNI) is a great challenge for regenerative medicine. Nerve autograft is the gold standard for clinical PNI repair. Due to its significant drawbacks, artificial nerve guidance conduits (NGCs) have drawn much attention as replacement therapies. We developed a combinatorial NGC consisting of longitudinally aligned electrospun nanofibers and porcine decellularized nerve matrix hydrogel (pDNM gel). The in vivo capacity for facilitating nerve tissue regeneration and functional recovery was evaluated in a rat sciatic nerve defect model.Methods: Poly (L-lactic acid) (PLLA) was electrospun into randomly oriented (PLLA-random) and longitudinally aligned (PLLA-aligned) nanofibers. PLLA-aligned were further coated with pDNM gel at concentrations of 0.25% (PLLA-aligned/0.25% pDNM gel) and 1% (PLLA-aligned/1% pDNM gel). Axonal extension and Schwann cells migration were evaluated by immunofluorescence staining of dorsal root ganglia cultured on the scaffolds. To fabricate implantable NGCs, the nanofibrous scaffolds were rolled and covered with an electrospun protection tube. The fabricated NGCs were then implanted into a 5 mm sciatic nerve defect model in adult male Sprague-Dawley rats. Nerves treated with NGCs were compared to contralateral uninjured nerves (control group), injured but untreated nerves (unstitched group), and autografted nerves. Nerve regeneration was monitored by an established set of assays, including T2 values and diffusion tensor imaging (DTI) derived from multiparametric magnetic resonance imaging (MRI), histological assessments, and immunostaining. Nerve functional recovery was evaluated by walking track analysis.Results: PLLA-aligned/0.25% pDNM gel scaffold exhibited the best performance in facilitating directed axonal extension and Schwann cells migration in vitro due to the combined effects of the topological cues provided by the aligned nanofibers and the biochemical cues retained in the pDNM gel. Consistent results were obtained in animal experiments with the fabricated NGCs. Both the T2 and fractional anisotropy values of the PLLA-aligned/0.25% pDNM gel group were the closest to those of the autografted group, and returned to normal much faster than those of the other NGCs groups. Histological assessment indicated that the implanted PLLA-aligned/0.25% pDNM gel NGC resulted in the largest number of axons and the most extensive myelination among all fabricated NGCs. Further, the PLLA-aligned/0.25% pDNM gel group exhibited the highest sciatic nerve function index, which was comparable to that of the autografted group, at 8 weeks post-surgery.Conclusions: NGCs composed of aligned PLLA nanofibers decorated with 0.25% pDNM gel provided both topological and biochemical guidance for directing and promoting axonal extension, nerve fiber myelination, and functional recovery. Moreover, T2-mapping and DTI metrics were found to be useful non-invasive monitoring techniques for PNI treatment.

Mesenchymal stem cell treatment for peripheral nerve injury: a narrative review.

Peripheral nerve injuries occur as the result of sudden trauma and lead to reduced quality of life. The peripheral nervous system has an inherent capability to regenerate axons. However, peripheral nerve regeneration following injury is generally slow and incomplete that results in poor functional outcomes such as muscle atrophy. Although conventional surgical procedures for peripheral nerve injuries present many benefits, there are still several limitations including scarring, difficult accessibility to donor nerve, neuroma formation and a need to sacrifice the autologous nerve. For many years, other therapeutic approaches for peripheral nerve injuries have been explored, the most notable being the replacement of Schwann cells, the glial cells responsible for clearing out debris from the site of injury. Introducing cultured Schwann cells to the injured sites showed great benefits in promoting axonal regeneration and functional recovery. However, there are limited sources of Schwann cells for extraction and difficulties in culturing Schwann cells in vitro. Therefore, novel therapeutic avenues that offer maximum benefits for the treatment of peripheral nerve injuries should be investigated. This review focused on strategies using mesenchymal stem cells to promote peripheral nerve regeneration including exosomes of mesenchymal stem cells, nerve engineering using the nerve guidance conduits containing mesenchymal stem cells, and genetically engineered mesenchymal stem cells. We present the current progress of mesenchymal stem cell treatment of peripheral nerve injuries.

Decellularized nerve matrix hydrogel scaffolds with longitudinally oriented and size-tunable microchannels for peripheral nerve regeneration

The scaffolding biomaterials and their internal structures are crucial in constructing growth-permissive microenvironment for tissue regeneration. A functional bioscaffold not only requires sufficient extracellular matrix components, but also provides topological guidance by mimicry of the ultrastructure of the native tissue. In our laboratory, a decellularized nerve matrix hydrogel derived from porcine sciatic nerve (pDNM-G) is successfully prepared, which shows great promise for peripheral nerve regeneration. Herein, longitudinally oriented microchannel structures were introduced into pDNM-G bioscaffolds (A-pDNM-G) through controlled unidirectional freeze-drying. The axially aligned microchannels effectively directed and significantly promoted neurite extension and Schwann cell migration, assessed by culturing dorsal root ganglion explants on the longitudinal sections of A-pDNM-G scaffolds. Such regenerative cellular responses can be further optimized by tuning the channel sizes. In vivo studies confirmed that the implanted nerve guidance conduits containing A-pDNM-G scaffolds significantly facilitated axonal extension, myelination, and reached considerable functional recovery in 15-mm rat sciatic nerve defects. The incorporation of nerve growth factor further improved the overall performance in the grafted nerve. The bioactive pDNM-G enables controlled release of neurotrophic factor and easy integration of topological cue provided by the axially aligned microchannels into implantable bioscaffolds, which may serve in future clinical treatments of peripheral nerve injury.

Electrospun conductive nanofiber yarns for accelerating mesenchymal stem cells differentiation and maturation into Schwann cell-like cells under a combination of electrical stimulation and chemical induction

Development of multifunctional tube-filling materials is required to improve the performances of the existing nerve guidance conduits (NGCs) in the repair of long-gap peripheral nerve (PN) injuries. In this study, composite nanofiber yarns (NYs) based on poly(p-dioxanone) (PPDO) biopolymer and different concentrations of carbon nanotubes (CNTs) were manufactured by utilizing a modified electrospinning apparatus. We confirmed the successful incorporation of CNTs into the PPDO nanofibers of as-fabricated composite NYs. The PPDO/CNT NYs exhibited similar morphology and structure in comparison with pure PPDO NYs. However, the PPDO/CNT NYs showed obviously enhanced mechanical properties and electrical conductivity compared to PPDO NYs. The biological tests revealed that the addition of CNTs had no negative effects on the cell growth, and proliferation of rabbit Schwann cells (rSCs), but it better maintained the phenotype of rSCs. We also demonstrated that the electrical stimulation (ES) significantly enhanced the differentiation capability of human adipose-derived mesenchymal stem cells (hADMSCs) into SC-like cells (SCLCs) on the PPDO/CNT NYs. More importantly, a unique combination of ES and chemical induction was found to further enhance the maturation of hADMSC-SCLCs on the PPDO/CNT NYs by notably upregulating the expression levels of SC myelination-associated gene markers and increasing the growth factor secretion. Overall, this study showed that our electrically conductive PPDO/CNT composite NYs could provide a beneficial microenvironment for various cell activities, making them an attractive candidate as NGC-infilling substrates for PN regeneration applications. STATEMENT OF SIGNIFICANCE: The morphology, microstructure, and bioelectrical properties of conductive PPDO/CNT NYs have been explored for guiding or controlling cell behaviors. The PPDO/CNT NYs exhibited improved mechanical properties and increased electrical conductivity compared to the CNT-free PPDO NYs. They also presented an obviously enhanced biocompatibility by effectively maintaining the phenotype of rSCs. In addition, when hADMSCs were seeded and cultured on the conductive PPDO/CNT NYs, CI was demonstrated to promote the SC-related growth factor secretion of hADMSCs, and ES was demonstrated to improve the phenotypic maturation of hADMSCs into myelinating SCLCs. Moreover, the combination of CI and ES was found to further synergistically enhance the maturation of hADMSC-SCLCs. The achievement of conductive PPDO/CNT NYs shows potential for application as NGC-infilling substrates for PN regeneration.

Cell-encapsulated chitosan-collagen hydrogel hybrid nerve guidance conduit for peripheral nerve regeneration.

Nerve guidance conduits (NGCs) composed of biocompatible polymers have been attracting attention as an alternative for autograft surgery in peripheral nerve regeneration. However, the nerve tissues repaired by NGCs often tend to be inadequate and lead to functional failure because of the lack of cellular supports. This paper presents a chitosan-collagen hydrogel conduit containing cells to induce peripheral nerve regeneration with cellular support. The conduit composed of two coaxial hydrogel layers of chitosan and collagen is simply made by molding and mechanical anchoring attachment with holes made on the hydrogel tube. A chitosan layer strengthens the conduit mechanically, and a collagen layer provides a scaffold for cells supporting the axonal extension. The conduits of different diameters (outer diameter approximately 2-4mm) are fabricated. The conduit is bioabsorbable with lysozyme, and biocompatible even under bio absorption. In the neuron culture demonstration, the conduit containing Schwann cells induced the extension of the axon of neurons directed to the conduit. Our easily fabricated conduit could help the high-quality regeneration of peripheral nerves and contribute to the nerve repair surgery.

Advances and clinical challenges for translating nerve conduit technology from bench to bed side for peripheral nerve repair.

Injuries to the peripheral nervous system remain a large-scale clinical problem. These injuries often lead to loss of motor and/or sensory function that significantly affects patients' quality of life. The current neurosurgical approach for peripheral nerve repair involves autologous nerve transplantation, which often leads to clinical complications. The most pressing need is to increase the regenerative capacity of existing tubular constructs in the repair of large nerve gaps through development of tissue-engineered approaches that can surpass the performance of autografts. To fully realize the clinical potential of nerve conduit technology, there is a need to reconsider design strategies, biomaterial selection, fabrication techniques and the various potential modifications to optimize a conduit microenvironment that can best mimic the natural process of regeneration. In recent years, a significant progress has been made in the designing and functionality of bioengineered nerve conduits to bridge long peripheral nerve gaps in various animal models. However, translation of thiswork from lab to commercial scale has not been achieve. The current review summarizes recent advances in the development of tissue engineered nerve guidance conduits (NGCs) with regard to choice of material, novel fabrication methods, surface modifications and regenerative cues such as stem cells and growth factors to improve regeneration performance. Also, the current clinical potential and future perspectives to achieve therapeutic benefits of NGCs will be discussed in context of peripheral nerve regeneration.

Elastin-like Proteins to Support Peripheral Nerve Regeneration in Guidance Conduits.

Synthetic nerve guidance conduits (NGCs) offer an alternative to harvested nerve grafts for treating peripheral nerve injury (PNI). NGCs have been made from both naturally derived and synthesized materials. While naturally derived materials typically have an increased capacity for bioactivity, synthesized materials have better material control, including tunability and reproducibility. Protein engineering is an alternative strategy that can bridge the benefits of these two classes of materials by designing cell-responsive materials that are also systematically tunable and consistent. Here, we tested a recombinantly derived elastin-like protein (ELP) hydrogel as an intraluminal filler in a rat sciatic nerve injury model. We demonstrated that ELPs enhance the probability of forming a tissue bridge between the proximal and distal nerve stumps compared to an empty silicone conduit across the length of a 10 mm nerve gap. These tissue bridges have evidence of myelinated axons, and electrophysiology demonstrated that regenerated axons innervated distal muscle groups. Animals implanted with an ELP-filled conduit had statistically higher functional control at 6 weeks than those that had received an empty silicone conduit, as evaluated by the sciatic functional index. Taken together, our data support the conclusion that ELPs support peripheral nerve regeneration in acute complete transection injuries when used as an intraluminal filler. These results support the further study of protein engineered recombinant ELP hydrogels as a reproducible, off-the-shelf alternative for regeneration of peripheral nerves.

Graphene-based conductive fibrous scaffold boosts sciatic nerve regeneration and functional recovery upon electrical stimulation

Peripheral nerve injury (PNI) is a very common consequence of traumatic injury and may cause serious disturbance in mediating functions in the human body. It's an urgent issue to promote the sufficient morphologic and functional regeneration of injured peripheral nerve. In this study, combination of graphene-based conductive fibrous scaffold (GCFS) and exogenous electrical stimulation (ES) were developed as an effective strategy to repair PNI, and the possible mechanisms underlying nerve recovery were further explored. The prepared GCFSs without or with 1.0 wt% graphene possessed electrical conductivity of 5.27 × 10−6 S/m and 3.12 S/m, respectively. The in vitro studies showed that ES could accelerate migration of rat mesenchymal stem cells (MSCs) seeded on the GCFS, promote the secretion of neurotrophic factors, and meanwhile up-regulate gene and protein expressions of neural markers. In vivo studies using a rat sciatic nerve injure model revealed that ES could significantly enhance sciatic nerve regeneration and functional recovery after implantation of GCFS nerve guidance conduit, and the daily ES exhibited repair-promoting capacity comparable to the gold standard autograft. Fundamentally, ES facilitated nerve regeneration maybe partly by the recruitment of endogenous MSCs and modulation of macrophage phenotypes. Taken together, GCFS combined with ES present a feasibility strategy to promote regeneration and functional recovery of the injured peripheral nerve.

Tracing Carbon Nanotubes (CNTs) in Rat Peripheral Nerve Regenerated with Conductive Conduits Composed of Poly(lactide-co-glycolide) and Fluorescent CNTs.

Nerve regeneration can be promoted using nerve guide conduits (NGCs). Carbon nanotubes (CNTs) are often used to prepare conductive NGCs, however, the major concern for their applications is the final location of the implanted CNTs in vivo. Herein, photoluminescent multiwalled CNTs (MWCNTs) were prepared and electrospun with poly(lactide-co-glycolide) (PLGA), followed by shaping into multichannel NGCs for repairing of injured rat sciatic nerve, thereby the distribution of CNTs in vivo could be detected via bioimaging. Photoluminescent MWCNTs (MWCNT-FITC) were prepared by functionalization with poly(glycidyl methacrylate) (PGMA) and fluorescein-isothiocyanate-isomer I (FITC) subsequently. The conductivity of the PLGA/MWCNT-FITC fibers was approx. 10-4 S/cm at 3 wt % MWCNTs. Compared with PLGA fibers, Schwann cells on PLGA/MWCNT-FITC fibers matured at a faster rate, accordingly, nerve regeneration was promoted by the PLGA/MWCNT-FITC NGC. With a confocal laser scanning microscope and small-animal imaging system, the location of MWCNTs was detected. Alongside the degradation of PLGA, MWCNTs intended to aggregate and were entrapped in the regenerated nerve tissue without migrating into surrounding tissues and other organs (liver, kidneys, and spleen). This study provides a useful characterization method for MWCNTs and the guidance for in vivo applications of MWCNTs in tissue engineering.

Regeneration of Rat Sciatic Nerve Using PLGA Conduit Containing Rat ADSCs with Controlled Release of BDNF and Gold Nanoparticles.

Implantation of a nerve guidance conduit (NGC) carrying neuroprotective factors is promising for repairing peripheral nerve injury. Here, we developed a novel strategy for repairing peripheral nerve injury by gold nanoparticles (AuNPs) and brain-derived neurotrophic factor (BDNF)-encapsulated chitosan in laminin-coated nanofiberof Poly(l-lactide-co-glycolide) (PLGA) conduit and transplantation of rat adipose-derived stem cells (r-ADSCs) suspended in alginate. Then, the beneficial effect of AuNPs, BDNF, and r-ADSCs on nerve regeneration was evaluated in rat sciatic nerve transection model. In vivo experiments showed that the combination of AuNPs- and BDNF-encapsulated chitosan nanoparticles in laminin-coated nanofiberof PLGA conduit with r-ADSCs could synergistically facilitate nerve regeneration. Furthermore, the in vivo histology, immunohistochemistry, and behavioral results demonstrated that the AuNPs- and BDNF-encapsulated chitosan nanoparticles in NGC could significantly reinforce the repair performance of r-ADSCs, which may also contribute to the therapeutic outcome of the AuNPs, BDNF, and r-ADSCs strategies. In this study, we found that the combination of AuNPs and BDNF releases in NGC with r-ADSCs may represent a new potential strategy for peripheral nerve regeneration.

Biomimetic and hierarchical nerve conduits from multifunctional nanofibers for guided peripheral nerve regeneration

Development of a functional nerve conduit to replace autografts remains a significant challenge particularly considering the compositional complexity and structural hierarchy of native peripheral nerves. In the present study, a multiscale strategy was adopted to fabricate 3D biomimetic nerve conduit from Antheraea pernyi silk fibroin (ApF)/(Poly(L-lactic acid-co-caprolactone)) (PLCL)/graphene oxide (GO) (ApF/PLCL/GO) nanofibers via nanofiber dispersion, template-molding, freeze-drying and crosslinking. The resultant conduits exhibit parallel multichannels (ϕ = 125 µm) surrounded by biomimetic fibrous fragments with tailored degradation rate and improved mechanical properties in comparison with the scaffold without GO. In vitro studies showed that such 3D biomimetic nerve scaffolds had the ability to offer an effective guiding interface for neuronal cell growth. Furthermore, these conduits showed a similarity to autografts in vivo repairing sciatic nerve defects based on a series of analysis (walking track, triceps weight, morphogenesis, vascularization, axonal regrowth and myelination). The conduits almost completely degraded within 12 weeks. These findings demonstrate that the 3D hierarchical nerve guidance conduit (NGC) with fascicle-like structure have great potential for peripheral nerve repair.

Polymeric Guide Conduits for Peripheral Nerve Tissue Engineering.

Peripheral nerve injuries (PNIs) are usually caused by trauma, immune diseases, and genetic factors. Peripheral nerve injury (PNI) may lead to limb numbness, muscle atrophy, and loss of neurological function. Although an abundance of theories have been proposed, very few treatments can effectively lead to complete recovery of neurological function. Autologous nerve transplantation is currently the gold standard. Nevertheless, only 50% of all patients were successfully cured using this method. In addition, it causes inevitable damage to the donor site, and available donor sites in humans are very limited. Tissue engineering has become a research hotspot aimed at achieving a better therapeutic effect from peripheral nerve regeneration. Nerve guide conduits (NGCs) show great potential in the treatment of PNI. An increasing number of scaffold materials, including natural and synthetic polymers, have been applied to fabricate NGCs for peripheral nerve regeneration. This review focuses on recent nerve guide conduit (NGC) composite scaffold materials that are applied for nerve tissue engineering. Furthermore, the development tendency of NGCs and future areas of interest are comprehensively discussed.

Additive Manufacturing of Nerve Guidance Conduits for Regeneration of Injured Peripheral Nerves.

As a common and frequent clinical disease, peripheral nerve defect has caused a serious social burden, which is characterized by poor curative effect, long course of treatment and high cost. Nerve autografting is first-line treatment of peripheral nerve injuries (PNIs) but can result in loss of function of the donor site, neuroma formation, and prolonged operative time. Nerve guidance conduit (NGC) serves as the most promising alternative to autologous transplantation, but its production process is complicated and it is difficult to effectively combine growth factors and bioactive substances. In recent years, additive manufacturing of NGCs has effectively solved the above problems due to its simple and efficient manufacturing method, and it can be used as the carrier of bioactive substances. This review examines recent advances in additive manufacture of NGCs for PNIs as well as insight into how these approaches could be improved in future studies.

Schwann Cell-Like Cells: Origin and Usability for Repair and Regeneration of the Peripheral and Central Nervous System.

Functional recovery after neurotmesis, a complete transection of the nerve fiber, is often poor and requires a surgical procedure. Especially for longer gaps (>3 mm), end-to-end suturing of the proximal to the distal part is not possible, thus requiring nerve graft implantation. Artificial nerve grafts, i.e., hollow fibers, hydrogels, chitosan, collagen conduits, and decellularized scaffolds hold promise provided that these structures are populated with Schwann cells (SC) that are widely accepted to promote peripheral and spinal cord regeneration. However, these cells must be collected from the healthy peripheral nerves, resulting in significant time delay for treatment and undesired morbidities for the donors. Therefore, there is a clear need to explore the viable source of cells with a regenerative potential similar to SC. For this, we analyzed the literature for the generation of Schwann cell-like cells (SCLC) from stem cells of different origins (i.e., mesenchymal stem cells, pluripotent stem cells, and genetically programmed somatic cells) and compared their biological performance to promote axonal regeneration. Thus, the present review accounts for current developments in the field of SCLC differentiation, their applications in peripheral and central nervous system injury, and provides insights for future strategies.

Bioinspired Multichannel Nerve Guidance Conduit Based on Shape Memory Nanofibers for Potential Application in Peripheral Nerve Repair.

Repairing peripheral nerve injury, especially long-range defects of thick nerves, is a great challenge in the clinic due to their limited regeneration capability. Most FDA-approved nerve guidance conduits with large hollow lumen are only suitable for short lesions, and their effects are unsatisfactory in repairing long gaps of thick nerves. Multichannel nerve guidance conduits have been shown to offer better regeneration of long nerve defects. However, existing approaches of fabricating multichannel nerve conduits are usually complicated and time-consuming. Inspired by the intelligent responsive shaping process of shape memory polymers, in this study, a self-forming multichannel nerve guidance conduit with topographical cues was constructed based on a degradable shape memory PLATMC polymer. With an initial tubular shape obtained by a high-temperature molding process, the electrospun shape memory nanofibrous mat could be temporarily formed into a planar shape for cell loading to realize the uniform distribution of cells. Then triggered by a physical temperature around 37 °C, it could automatically restore its permanent tubular shape to form the multichannel conduit. This multichannel conduit exhibits better performance in terms of cell growth and the repair of rat sciatic nerve defects. These results reveal that self-forming nerve conduits can be realized based on shape memory polymers; thus, the fabricated bioinspired multichannel nerve guidance conduit has great potential in peripheral nerve regeneration.

Electrically Conductive Hydrogel Nerve Guidance Conduits for Peripheral Nerve Regeneration

AbstractPeripheral nerve injuries are serious conditions, and surgical treatment has critical limitations. Therefore, nerve guidance conduits (NGCs) are proposed as an alternative. In this study, multifunctional NGCs are fabricated for the regeneration of injured peripheral nerves. Graphene oxide (GO) and gelatin‐methacrylate (GelMA) are polymerized and chemically reduced to form reduced (GO/GelMA) (r(GO/GelMA)). The prepared materials present good electrical conductivity, flexibility, mechanical stability, and permeability, which are suitable for use as NGCs. In vitro studies show 2.1‐ and 1.4‐fold promotion of neuritogenesis of PC12 neuronal cells on r(GO/GelMA) compared to GelMA and unreduced GO/GelMA, respectively. Animal studies using a rat sciatic nerve injury model with a 10 mm gap between the proximal and distal regions of the defect reveal that r(GO/GelMA) NGCs significantly enhance peripheral nerve regeneration, indicated by improved muscle weight increase, electro‐conduction velocity, and sciatic nerve function index. Specifically, r(GO/GelMA) NGCs are utilized to potentiate regrowth with myelination in rat sciatic nerves followed by histological, immunohistological, and morphometrical analyses. This study successfully shows the feasibility of electrically conductive hydrogel NGCs as functional conduits for improved nerve regeneration in a preclinical study, where these NGCs can not only mimic nerve tissues but also strongly promote nerve regeneration.

Electrospinning Multilayered Scaffolds Loaded with Melatonin and Fe3O4 Magnetic Nanoparticles for Peripheral Nerve Regeneration

AbstractPeripheral nerve injury is a common clinical problem bringing heavy burden to patients, due to its high incidence and unsatisfactory treatment. Nerve guidance conduit (NGC) is a promising scaffold for peripheral nerve repair, and bioactive agents are applied for great functional recovery. Melatonin (MLT) and Fe3O4 magnetic nanoparticles (Fe3O4‐MNPs) are proven to inhibit oxidative stress, inflammation, and induce nerve regeneration. Herein, a multilayered composite NGC loaded with MLT and Fe3O4‐MNPs is designed for sequential and sustainable drug release, creating an appropriate microenvironment for nerve regeneration. The composite scaffold shows sufficient mechanical strength and biocompatibility in vitro, and evidently promotes morphological, functional, and electrophysiological recovery of regenerated sciatic nerves in vivo. This work proves that the multilayered conduits show great prospect in the long‐term nerve defects treatment due to easy manufacture and desired efficacy.

Development of a Piezoelectric PVDF-TrFE Fibrous Scaffold to Guide Cell Adhesion, Proliferation, and Alignment.

Severe peripheral nervous system injuries currently hold limited therapeutic solutions. Existing clinical techniques such as autografts, allografts, and newer nerve guidance conduits have shown variable outcomes in functional recovery, adverse immune responses, and in some cases low or minimal availability. This can be attributed in part to the lack of chemical, physical, and electrical cues directing both nerve guidance and regeneration. To address this pressing clinical issue, electrospun nanofibers and microfibers composed of piezoelectric polyvinylidene flouride-triflouroethylene (PVDF-TrFE) have been introduced as an alternative template for tissue engineered biomaterials, specifically as it pertains to their relevance in soft tissue and nerve repair. Here, biocompatible scaffolds of PVDF-TrFE are fabricated and their ability to generate an electrical response to mechanical deformations and produce a suitable regenerative microenvironment is examined. It is determined that 20% (w/v) PVDF-TrFE in (6:4) dimethyl formamide (DMF):acetone solvent maintains a desirable piezoelectric coefficient and the proper physical and electrical characteristics for tissue regeneration. Further, it is concluded that scaffolds of varying thickness promoted the adhesion and alignment of Schwann cells and fibroblasts. This work offers a prelude to further advancements in nanofibrous technology and a promising outlook for alternative, autologous remedies to peripheral nerve damage.

Micro-grooved nerve guidance conduits combined with microfiber for rat sciatic nerve regeneration

In order to accelerate the regeneration of injured nerves, highly aligned structures that mimic native tissues are essential for nerve guidance conduits (NGC). In this study, a biodegradable porous micro-patterned NGCs were manufactured by use of capillary force lithography and salt leaching method, which filled as wrapped with aligned electrospun microfiber (PA-NGC) using. These combined NGC showed 5μm aligned groove pattern on the interior wall and were filled with 4–5μm align fibers for a fascicular structure to mimic the native nerve. The highly aligned structure has increased PC12 migration and morphological elongation compared with random microfiber. For the in vivo study, we bridged in the 10mm sciatic nerve defect margins with NGC. The PA-NGC were compared to flat NGCs filled with random (FR-NGC) or aligned fiber (FA-NGC) and patterned NGCs filled with random fiber (PR-NGC). The PA-NGC showed as dramatically re-bridged neurofilament and higher sciatic function index, onset-to-peak of amplitude, muscle weight and fiber diameter compared to other groups after 8 weeks of implantation. In our results, the PA-NGC not only can serve as a design for functional NGC without growth factor but also can be used in clinical application for peripheral nerve regeneration.

CNT/Sericin Conductive Nerve Guidance Conduit Promotes Functional Recovery of Transected Peripheral Nerve Injury in a Rat Model.

Peripheral nerve injury usually leads to poor outcomes such as painful neuropathies and disabilities. Autogenous nerve grafting is the current gold standard; however, the limited source of a donor nerve remains a problem. Numerous tissue engineering nerve guidance conduits have been developed as substitutes for autografts. However, a few conduits can achieve the reparative effect equivalent to autografts. Here, we report for the development and application of a carbon nanotube (CNT)/sericin nerve conduit with electrical conductivity and suitable mechanical properties for nerve repair. This CNT/sericin conduit possesses favorable properties including biocompatibility, biodegradability, porous microarchitecture, and suitable swelling property. We thus applied this conduit for bridging a 10 mm gap defect of a transected sciatic nerve combined with electrical stimulation (ES) in a rat injury model. By the end of 12 weeks, we observed that the CNT/sericin conduit combined with electrical stimulation could effectively promote both structural repair and functional recovery comparable to those of the autografts, evidenced by the morphological and histological analyses, electrophysiological responses, functional studies, and target muscle reinnervation evaluations. These findings suggest that this electric conductive CNT/sericin conduit combined with electrical stimulation may have the potential to serve as a new alternative for the repair of transected peripheral nerves.