Nerve Guidance Conduits Research Articles

Combining external physical stimuli and nanostructured materials for upregulating pro-regenerative cellular pathways in peripheral nerve repair

Peripheral nerve repair remains a major clinical challenge, particularly in the pursuit of therapeutic approaches that ensure adequate recovery of patient’s activity of daily living. Autografts are the gold standard in clinical practice for restoring lost sensorimotor functions nowadays. However, autografts have notable drawbacks, including dimensional mismatches and the need to sacrifice one function to restore another. Engineered nerve guidance conduits have therefore emerged as promising alternatives. While these conduits show surgical potential, their clinical use is currently limited to the repair of minor injuries, as their ability to reinnervate limiting gap lesions is still unsatisfactory. Therefore, improving patient functional recovery requires a deeper understanding of the cellular mechanisms involved in peripheral nerve regeneration and the development of therapeutic strategies that can precisely modulate these processes. Interest has grown in the use of external energy sources, such as light, ultrasound, electrical, and magnetic fields, to activate cellular pathways related to proliferation, differentiation, and migration. Recent research has explored combining these energy sources with tailored nanostructured materials as nanotransducers to enhance selectivity towards the target cells. This review aims to present the recent findings on this innovative strategy, discussing its potential to support nerve regeneration and its viability as an alternative to autologous transplantation.

An Easy-to-Handle Route for Bicomponent Porous Tubes Fabrication as Nerve Guide Conduits

Over the past two decades, the development of nerve guide conduits (NGCs) has gained much attention due to the impellent need to find innovative strategies to take care of damaged or degenerated peripheral nerves in clinical surgery. In this view, significant effort has been spent on the development of high-performance NGCs by different materials and manufacturing approaches. Herein, a highly versatile and easy-to-handle route to process 3D porous tubes made of chitosan and gelatin to be used as a nerve guide conduit were investigated. This allowed us to fabricate highly porous substrates with a porosity that ranged from 94.07 ± 1.04% to 97.23 ± 1.15% and average pore sizes—estimated via X-ray computed tomography (XCT) reconstruction and image analysis—of hundreds of microns and an irregular shape with an aspect ratio that ranged from 0.70 ± 0.19 to 0.80 ± 0.15 as a function of the chitosan/gelatin ratio. More interestingly, the addition of gelatin allowed us to modulate the mechanical properties, which gradually reduced the stiffness—max strength from 0.634 ± 0.015 MPa to 0.367 ± 0.021 MPa—and scaffold toughness—from 46.2 kJ/m3 to 14.0 kJ/m3—as the gelatin content increased. All these data fall into the typical ranges of the morphological and mechanical parameters of currently commercialized NGC products. Preliminary in vitro studies proved the ability of 3D porous tubes to support neuroblastoma cell (SH-SY5Y) adhesion and proliferation. In perspective, the proposed approach could also be easily implemented with the integration of other processing techniques (e.g., electrospinning) for the design of innovative bi-layered systems with an improved cell interface and molecular transport abilities.

In Vitro Models for Peripheral Nerve Regeneration.

Peripheral nerve injury (PNI) resulting in lesions is highly prevalent clinically, but current therapeutic approaches fail to provide satisfactory outcomes in many patients. While peripheral nerves have intrinsic regenerative capacity, the regenerative capabilities of peripheral nerves are often insufficient to restore full functionality. This highlights an unmet need for developing more effective strategies to repair damaged peripheral nerves and improve regenerative success. Consequently, researchers are actively exploring a variety of therapeutic strategies, encompassing the local delivery of trophic factors or bioactive molecules, the design of advanced biomaterials that interact with regenerating axons, and augmentation with nerve guidance conduits or complex prostheses. However, clinical translation of these technologies remains limited, emphasizing the need for continued research on peripheral nerve regeneration modalities that can enhance functional restoration. Experimental models that accurately recapitulate key aspects of peripheral nerve injury and repair biology can accelerate therapeutic development by enabling systematic testing of new techniques. Advancing regenerative therapies for PNI requires bridging the gap between basic science discoveries and clinical application. This review discusses different in vitro models of peripheral nerve injury and repair, including their advantages, limitations, and potential applications.

Pre-clinical evaluation of advanced nerve guide conduits using a novel 3D in vitro testing model.

Autografts are the current gold standard for large peripheral nerve defects in clinics despite the frequently occurring side effects like donor site morbidity. Hollow nerve guidance conduits (NGC) are proposed alternatives to autografts, but failed to bridge gaps exceeding 3 cm in humans. Internal NGC guidance cues like microfibres are believed to enhance hollow NGCs by giving additional physical support for directed regeneration of Schwann cells and axons. In this study, we report a new 3D in vitro model that allows the evaluation of different intraluminal fibre scaffolds inside a complete NGC. The performance of electrospun polycaprolactone (PCL) microfibres inside 5 mm long polyethylene glycol (PEG) conduits were investigated in neuronal cell and dorsal root ganglion (DRG) cultures in vitro. Z-stack confocal microscopy revealed the aligned orientation of neuronal cells along the fibres throughout the whole NGC length and depth. The number of living cells in the centre of the scaffold was not significantly different to the tissue culture plastic (TCP) control. For ex vivo analysis, DRGs were placed on top of fibre-filled NGCs to simulate the proximal nerve stump. In 21 days of culture, Schwann cells and axons infiltrated the conduits along the microfibres with 2.2 ± 0.37 mm and 2.1 ± 0.33 mm, respectively. We conclude that this in vitro model can help define internal NGC scaffolds in the future by comparing different fibre materials, composites and dimensions in one setup prior to animal testing.

A tacrolimus-eluting nerve guidance conduit enhances regeneration in acritical-sized peripheral nerve injury rat model.

Critical-sized peripheral nerve injuries pose a significant clinical challenge and lead to functional loss and disability. Current regeneration strategies, including autografts, synthetic nerve conduits, and biologic treatments, encounter challenges such as limited availability, donor site morbidity, suboptimal recovery, potential immune responses, and sustained stability and bioactivity. An obstacle in peripheral nerve regeneration is the immune response that can lead to inflammation and scarring that impede the regenerative process. Addressing both the immunological and regenerative needs is crucial for successful nerve recovery. Here, we introduce a novel biodegradable tacrolimus-eluting nerve guidance conduit engineered from a blend of poly (L-lactide-co-caprolactone) to facilitate peripheral nerve regeneration and report the testing of this conduit in 15-mm critical-sized gaps in the sciatic nerve of rats. The conduit's diffusion holes enable the local release of tacrolimus, a potent immunosuppressant with neuro-regenerative properties, directly into the injury site. A series of in vitro experiments were conducted to assess the ability of the conduit to maintain a controlled tacrolimus release profile that could promote neurite outgrowth. Subsequent in vivo assessments in rat models of sciatic nerve injury revealed significant enhancements in nerve regeneration, as evidenced by improved axonal growth and functional recovery compared to controls using placebo conduits. These findings indicate the synergistic effects of combining a biodegradable conduit with localized, sustained delivery of tacrolimus, suggesting a promising approach for treating peripheral nerve injuries. Further optimization of the design and long-term efficacy studies and clinical trials are needed before the potential for clinical translation in humans can be considered.

Review on potential nerve guidance conduits design for spinal cord injuries

The current treatment of spinal cord injuries (SCI) focuses mainly on the elimination of secondary damage to the central nervous system. The performance of treatments targeted at neurological recovery is not satisfactory. Inspired by the treatment of peripheral nerve injuries using tissue engineering, the nerve guidance conduits became one of the potential designs to improve the rate of neurological recovery among patients. With the proper design like multichannel and fabrication techniques like 3D bioprinting, the hybrid biomaterial may provide good guidance for nerves to grow in long gaps under well-picked neuromorphic factors. The new technologies including vascularization and electrical stimulation give more possibilities for the construction of treatment. New materials like shape-memory polymers may improve the fabrication of NGCs. However, the combination of these innovative findings was not performed for lab tests and clinical tests. The commercialization of NGC for SCI is also in need of better standardization and regulation. There may be a comprehensive NGC-based design for SCI emerging in the future which improves the performance of neurological recovery.

Fully biodegradable and self-powered nerve guidance conduit based on zinc-molybdenum batteries for peripheral nerve repair

Peripheral nerve injury (PNI) poses a significant public health issue, often leading to muscle atrophy and persistent neuropathic pain, which can drastically impact the quality of life for patients. Electrical stimulation represents an effective and non-pharmacological treatment to promote nerve regeneration. Yet, the postoperative application of electrical stimulation remains a challenge. Here, we propose a fully biodegradable, self-powered nerve guidance conduit (NGC) based on dissolvable zinc-molybdenum batteries. The conduit can offer topographic guidance for nerve regeneration and deliver sustained electrical cues between both ends of a transected nerve stump, extending beyond the surgical window. Schwann cell proliferation and adenosine triphosphate (ATP) production are enhanced by the introduction of the zinc-molybdenum batteries. In rodent models with 10-mm sciatic nerve damage, the device effectively enhances nerve regeneration and motor function recovery. This study offers innovative strategies for creating biodegradable and electroactive devices that hold important promise to optimize therapeutic outcomes for nerve regeneration.

Efficacy of 3D printed anatomically equivalent thermoplastic polyurethane guide conduits in promoting the regeneration of critical-sized peripheral nerve defects.

Three-dimensional (3D) printing is an emerging tool for creating patient-specific tissue constructs analogous to the native tissue microarchitecture. In this study, anatomically equivalent 3D nerve conduits were developed using thermoplastic polyurethane (TPU) by combining reverse engineering and material extrusion (i.e., fused deposition modeling) technique. Printing parameters were optimized to fabricate nerve-equivalent TPU constructs. The TPU constructs printed with different infill densities supported the adhesion, proliferation, and gene expression of neuronal cells. Subcutaneous implantation of the TPU constructs for three months in rats showed neovascularization with negligible local tissue inflammatory reactions and was classified as a non-irritant biomaterial as per ISO 10993-6. To perform in vivo efficacy studies, nerve conduits equivalent to rat's sciatic nerve were fabricated and bridged in a 10 mm sciatic nerve transection model. After four months of implantation, the sensorimotor function and histological assessments revealed that the 3D printed TPU conduits promoted the regeneration in critical-sized peripheral nerve defects equivalent to autografts. ThisstudyprovedthatTPU-based 3D printed nerve guidance conduits can be created to replicate the complicated features ofnaturalnerves that can promote the regeneration of peripheral nerve defects and also show the potential to be extended to several other tissues for regenerative medicine applications.&#xD.

Progress on application of hydrogels in the field of peripheral nerve injury repair

As one of the common traumatic diseases in clinical practice, peripheral nerve injury (PIN) often causes nerve pain, abnormal reflexes, autonomic disorders, and even sensorimotor disorders due to the slow regeneration rate after injury, which seriously affects body function. Even as the gold standard of treatment, autologous nerve transplantation has limitations such as limited donor area and donor injury, which greatly limits its clinical application effect. Therefore, the preparation of artificial nerve grafts suitable for clinical practice has become the future development trend of peripheral nerve injury treatment, and the repair of injury defects and the promotion of nerve regeneration have also become research hotspots in tissue engineering and regenerative medicine. In recent years, extensive research has been carried out on nerve guidance conduits (NGCs) in the field of nerve regeneration and repair, in which scaffold materials and internal fillers have also become the focus of research as the core elements of neural catheters, and a series of achievements have been made in the application of new materials, embedding stem cells/precursor cells, and developing trophic factors and drug-loaded sustained-release systems. Therefore, this paper focuses on the application progress of hydrogel and its related derivative materials in the field of peripheral nerve injury repair, and provides new ideas for promoting the related research of tissue engineering and clinical medicine.

Liquid metal neuro-electrical interface

Liquid metal (LM), an emerging functional material, plays increasing roles in biomedical and healthcare areas. It has particular values in neural interfaces as it combines high conductivity, flowability, and biocompatibility properties. Neuro-electrical interfaces (NEIs) are effective tools to provide a bridge between the nervous system and the outside world. The main target of developing neural interfaces is to help disabled people repair damaged nerves and enhance human capacity above normal ability. This article systematically summarizes LM-based neural interface technologies, including neural electrodes for electrical signal acquisition and administration of electrical stimulation and nerve guidance conduits for neural connectivity and functional reconstruction. The discussion begins with an overview of the fundamental properties associated with LM materials involved in the field of neural interface applications. The fabrication methods of LM-based neuro-electrodes and conduits are then introduced, and the current development status of LM-based neuro-electrodes and conduits is elaborated. Finally, the prospects and possible challenges of LM-based neural interfaces are outlined.

4D-Printed MXene-Based Artificial Nerve Guidance Conduit for Enhanced Regeneration of Peripheral Nerve Injuries.

Repairing larger defects (>5mm) in peripheral nerve injuries (PNIs) remains a significant challenge when using traditional artificial nerve guidance conduits (NGCs). A novel approach that combines 4D printing technology with poly(L-lactide-co-trimethylene carbonate) (PLATMC) and Ti3C2Tx MXene nanosheets is proposed, thereby imparting shape memory properties to the NGCs. Upon body temperature activation, the printed sheet-like structure can quickly self-roll into a conduit-like structure, enabling optimal wrapping around nerve stumps. This design enhances nerve fixation and simplifies surgical procedures. Moreover, the integration of microchannel expertly crafted through 4D printing, along with the incorporation of MXene nanosheets, introduces electrical conductivity. This feature facilitates the guided and directional migration of nerve cells, rapidly accelerating the healing of the PNI. By leveraging these advanced technologies, the developed NGCs demonstrate remarkable potential in promoting peripheral nerve regeneration, leading to substantial improvements in muscle morphology and restored sciatic nerve function, comparable to outcomes achieved through autogenous nerve transplantation.

Stereolithography 3D printing of microgroove master moulds for topography-induced nerve guidance conduits

 Patients who have peripheral nerve damage from trauma or disease may suffer lifelong disability. Current interventions such as nerve allografts are inadequate due to limited availability of tissue and donor-site morbidity. Commercial nerve guidance conduits are used to bridge the damaged nerve gap and restore function. Typically, however, they lack cell-instructive guidance cues to promote directed regeneration. Tissue-engineered nerve guidance conduits that utilise micro- and nano-topographical architectures have been demonstrated to direct cell behaviour and contact guidance. This study uses projection micro-stereolithography-based three-dimensional (3D) printing to fabricate microgrooved (10–30 μm) master moulds to produce polydimethylsiloxane (PDMS) moulds and solvent cast polycaprolactone and polylactic acid films. The polymer microgrooves were successfully fabricated and were able to be formed into tubular nerve guidance conduits. The surface morphology, roughness, wettability, and thermal properties of the films were characterised. The microgroove topography improved proliferation and induced alignment of SH-SY5Y cells. This facile 3D printing approach is promising for the fabrication of nerve guidance conduits with topographical guidance cues as it obviates the need for using photolithographic techniques. Thus, this approach provides an alternative that is simpler, faster, cheaper, and offers greater design freedom.

Shape-Persistent Conductive Nerve Guidance Conduits for Peripheral Nerve Regeneration.

To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.

Sea Cucumber-Inspired Microneedle Nerve Guidance Conduit for Synergistically Inhibiting Muscle Atrophy and Promoting Nerve Regeneration.

Muscle atrophy resulting from peripheral nerve injury (PNI) poses a threat to a patient's mobility and sensitivity. However, an effective method to inhibit muscle atrophy following PNI remains elusive. Drawing inspiration from the sea cucumber, we have integrated microneedles (MNs) and microchannel technology into nerve guidance conduits (NGCs) to develop bionic microneedle NGCs (MNGCs) that emulate the structure and piezoelectric function of sea cucumbers. Morphologically, MNGCs feature an outer surface with outward-pointing needle tips capable of applying electrical stimulation to denervated muscles. Simultaneously, the interior contains microchannels designed to guide the migration of Schwann cells (SCs). Physiologically, the incorporation of conductive reduced graphene oxide and piezoelectric zinc oxide nanoparticles into the polycaprolactone scaffold enhances conductivity and piezoelectric properties, facilitating SCs' migration, myelin regeneration, axon growth, and the restoration of neuromuscular function. These combined effects ultimately lead to the inhibition of muscle atrophy and the restoration of nerve function. Consequently, the concept of the synergistic effect of inhibiting muscle atrophy and promoting nerve regeneration has the capacity to transform the traditional approach to PNI repair and find broad applications in PNI repair.

Ultrasound-Responsive Aligned Piezoelectric Nanofibers Derived Hydrogel Conduits for Peripheral Nerve Regeneration.

Nerve guidance conduits (NGCs) are considered as promising treatment strategy and frontier trend for peripheral nerve regeneration, while their therapeutic outcomes are limited by the lack of controllable drug delivery and available physicochemical cues. Herein, novel aligned piezoelectric nanofibers derived hydrogel NGCs with ultrasound (US)-triggered electrical stimulation (ES) and controllable drug release for repairing peripheral nerve injury are proposed. The inner layer of the NGCs is the barium titanate piezoelectric nanoparticles (BTNPs)-doped polyvinylidene fluoride-trifluoroethylene [BTNPs/P(VDF-TrFE)] electrospinning nanofibers with improved piezoelectricity and aligned orientation. The outer side of the NGCs is the thermoresponsive poly(N-isopropylacrylamide) hybrid hydrogel with bioactive drug encapsulation. Such NGCs can not only induce neuronal-oriented extension and promote neurite outgrowth with US-triggered wireless ES, but also realize the controllable nerve growth factor release with the hydrogel shrinkage under US-triggered heating. Thus, the NGC can positively accelerate the functional recovery and nerve axonal regeneration of rat models with long sciatic nerve defects. It is believed that the proposed US-responsive aligned piezoelectric nanofibers derived hydrogel NGCs will find important applications in clinic neural tissue engineering.

Platelet Rich Fibrin Membrane as Nerve Guidance Conduit for Reconstruction Case with Nerve Repair Based Morphometric and Electrophysiologic Parameters: A Systematic Review and Meta-Analysis

Introduction: Motor or sensory nerve injury is a major surgical and clinical challenge, often with disappointing results and impairing sensory and motor function. Now there are some studies to looking for ways to accelerate nerve regeneration. Platelet-rich fibrin (PRF) is made from an autologous platelet concentrate that contains progenitor cells that are essential for the healing process, along with neurotrophic factors and several growth factors. Additionally, PRF can be manufactured in the membrane form that can be wrapped around nerves in the form of tubes which tubulation has many advantages such as guiding growth within the tubular shape to improve regenerative capacity. Methods: This systematic review and meta-analysis was conducted as per the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A systematic, detailed search was carried out by the authors in the electronic databases, including PubMed, Cochrane, Research Gate, Elsevier, and PRS Journal. Studies were selected and compared based on outcome measures like Morphometric (Axon Area and Myelin Sheath Thickness) and Electrophysiologic (Amplitude and Nerve Conduction Velocity). Statistical analysis was performed using a random- effect model, pooled standard mean difference and I2 heterogeneity. Result: Four randomized studies with analyzed 4 parameters, those are Morphometric (Axon Area and Myelin Sheath Thickness) and Electrophysiologic (Amplitude and Nerve Conduction Velocity). Pooled analysis for the outcome like Myelin Sheath Thickness, Axon Area, and Amplitude showed a significant result in groups with PRF. Pooled analysis for outcome of Nerve Conduction Velocity showed no significant difference between the groups with PRF and without PRF (SMD: 0.01; 95% CI: -0.64. 0.65) with P = 0.99. Conclusion: This Meta-analysis shows that PRF membrane as nerve guidance conduit is promising method and can improve function outcome in nerve repair specially in Morphometric and Electrophysiologic parameters but outcome of Nerve Conduction Velocity showed no significant in this study.

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve.

JOURNAL/nrgr/04.03/01300535-202506000-00029/figure1/v/2024-08-05T133530Z/r/image-tiff Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits (tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects (typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk+ tNGCs with the tubes without holes (silk- tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk+ tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk+ group was found compared with autologous nerve transplants and silk-, accompanied by improved axon regeneration at the distal coaptation point compared with the silk- tNGCs at 7 weeks postoperatively. In the 15-mm (critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk+ tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk+ tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

Electrical aligned polyurethane nerve guidance conduit modulates macrophage polarization and facilitates immunoregulatory peripheral nerve regeneration

Biomaterials can modulate the local immune microenvironments to promote peripheral nerve regeneration. Inspired by the spatial orderly distribution and endogenous electric field of nerve fibers, we aimed to investigate the synergistic effects of electrical and topological cues on immune microenvironments of peripheral nerve regeneration. Nerve guidance conduits (NGCs) with aligned electrospun nanofibers were fabricated using a polyurethane copolymer containing a conductive aniline trimer and degradable L-lysine (PUAT). In vitro experiments showed that the aligned PUAT (A-PUAT) membranes promoted the recruitment of macrophages and induced their polarization towards the pro-healing M2 phenotype, which subsequently facilitated the migration and myelination of Schwann cells. Furthermore, NGCs fabricated from A-PUAT increased the proportion of pro-healing macrophages and improved peripheral nerve regeneration in a rat model of sciatic nerve injury. In conclusion, this study demonstrated the potential application of NGCs in peripheral nerve regeneration from an immunomodulatory perspective and revealed A-PUAT as a clinically-actionable strategy for peripheral nerve injury.

Ultralong and highly axially aligned nerve guide conduits produced by electro-centrifugal spinning

The fabrication of nerve guide conduits (NGCs) with axially aligned fibers has been realized by electrospinning; however, the reported maximum length of such NGCs is limited to 2 cm which cannot repair a long injured peripheral nerve. In this context, a modified electro-centrifugal spinning (ECS) system is developed to produce ultralong and highly axially aligned NGCs. To this end, medical-grade poly (lactic-co-glycolic acid) PLGA with L-to-G ratios of 8/2, 7/3, and 5/5 loaded with antibiotic ciprofloxacin (CIP) are used to investigate the corresponding spinning mechanisms and drug release behaviors. Specifically speaking, first, the effects of chloroform/trifluoroethanol co-solvents and drug loading on the spinnability and fiber orientation of PLGA are systematically investigated, and tubular conduits are produced with the established method. Second, uniaxial tensile tests and cyclic compressive tests for the conduits with and without drug loading are conducted; PLGA conduits with an L-to-G ratio of 8/2 are further annealed to enhance their mechanical properties. Last, the drug release behavior of the conduits in vitro is studied. As a result, highly fiber-aligned NGCs with a length of over 10 cm, combined with excellent mechanical properties and well-controlled drug release features can be efficiently produced. Therefore, this work provides a practical strategy for producing NGCs with high efficiency.

Innovations in Peripheral Nerve Regeneration.

The field of peripheral nerve regeneration is a dynamic and rapidly evolving area of research that continues to captivate the attention of neuroscientists worldwide. The quest for effective treatments and therapies to enhance the healing of peripheral nerves has gained significant momentum in recent years, as evidenced by the substantial increase in publications dedicated to this field. This surge in interest reflects the growing recognition of the importance of peripheral nerve recovery and the urgent need to develop innovative strategies to address nerve injuries. In this context, this article aims to contribute to the existing knowledge by providing a comprehensive review that encompasses both biomaterial and clinical perspectives. By exploring the utilization of nerve guidance conduits and pharmacotherapy, this article seeks to shed light on the remarkable advancements made in the field of peripheral nerve regeneration. Nerve guidance conduits, which act as artificial channels to guide regenerating nerves, have shown promising results in facilitating nerve regrowth and functional recovery. Additionally, pharmacotherapy approaches have emerged as potential avenues for promoting nerve regeneration, with various therapeutic agents being investigated for their neuroprotective and regenerative properties. The pursuit of advancing the field of peripheral nerve regeneration necessitates persistent investment in research and development. Continued exploration of innovative treatments, coupled with a deeper understanding of the intricate processes involved in nerve regeneration, holds the promise of unlocking the complete potential of these groundbreaking interventions. By fostering collaboration among scientists, clinicians, and industry partners, we can accelerate progress in this field, bringing us closer to the realization of transformative therapies that restore function and quality of life for individuals affected by peripheral nerve injuries.