Nerve Graft Research Articles

Surgery for internal rotation contracture in infancy may obviate the need for brachial plexus nerve reconstruction: early experience

Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients, however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale (AMS) scores, Cookie Tests, and the requirement for subsequent neuroma resection and nerve grafting. Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie Test for elbow flexion. Thirteen patients either passed the Cookie Test or scored AMS 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie Test. Two patients did not have sufficient follow to assess elbow flexion. Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.

Is it possible to follow the risk of rupture after end-to-end nerve repairs in brachial plexus surgery? Technical note.

In traumatic and obstetric brachial plexus injuries, removal of the damaged nerve, repair with the nerve grafts, and nerve transfers are mostly preferred techniques. Success is directly proportional to surgical technique as it is known that end-to-end repair of the peripheral nerves gives better results. The greatest risk in end-to-end repair is the nerve rupture at the brachial plexus repair region and this cannot be detected by conventional radiological techniques. Brachial plexus injuries of obstetrical and traumatic patients were operated. If possible and at least one nerve was repaired end to end, follow-up of nerve continuity was done by titanium hemopclip insertion to both sides of the nerve repair area. A new technique nerve repair site marking was developed and end-to-end nerve repair continuity was followed simply by x-ray. This technique was used for end-to-end nerve coaptions of 38 obstetric and 40 traumatic brachial plexus injuries. Follow-up was done for 6 weeks. Every week patients sent the x-ray of the repair site. Only 3 patients had nerve repair site rupture, and revision surgery was done immediately. Nerve repair site marking technique and follow-up with only x-ray is a simple reliable, safe, and cheap method that can be applied to any end-to-end nerve repair. This technique has no morbidity or side effects. The aim of the study is to summarize or explain the nerve repair site marking technique used in the brachial plexus region.

Median to Radial Nerve Transfer: An 8-Year Experience From a Lower-Middle Income Country

IntroductionWith an incidence of 2-16%, radial nerve palsy is one of the common forms of nerve injuries globally. Radial nerve palsy causes debilitating effects including loss of elbow extension, wrist drop and loss of finger extension. Reparative surgical pathways range from primary repair and neurolysis, to nerve grafting, nerve transfers, and tendon transfers. Due to ease of performance and acceptability and reproducibility of outcomes, tendon transfers are considered the gold standard of radial nerve palsy repair. However, independent finger function cannot be achieved and as such may not give truly desirable results. In lower-middle income countries, the question of nerve transfer versus tendon transfer for patients who are keen to get back to work is key. While tendon transfer recovery is faster, the functional loss is often considered devastating for fine hand function due to loss of grip secondary to lack of wrist and finger extension. In this study, we present our experience of performing median nerve transfers for radial nerve palsy in Pakistan. MethodsWe performed a retrospective case-series of patients undergoing median to radial nerve transfer for radial nerve palsy over a period of 6 y, from 2012 to 2019. Patients with radial nerve palsy were diagnosed via electromyography and nerve conduction studies. The procedure involved coapting the branches of the flexor carpi radialis and flexor digitorum superficialis (long and ring finger) nerves to the posterior interosseous nerve and extensor carpi radialis brevis, respectively. Patients were assessed using the Medical Research Council scale for muscle strength of wrist, finger and thumb extension separately at 1 y time. Our results were then compared to results from similar nerve transfer studies. ResultsWe operated on 10 right-hand dominant patients, eight males and two females with a median age of 33 y (6-63 y). four sustained injury to the right hand and six to the left. Causes of the injuries included road traffic accident (n = 3), firearm injury (n = 4), shrapnel (n = 1), iatrogenic injury (injection in deltoid region (n = 1) and fall (n = 1). Types of fracture included mid humerus fracture, fracture of the surgical neck of the humerus, and supracondylar fracture of the humerus. Median time to surgery since injury was 4 mo (1-8 mo). Independent wrist extension was M4+ in all patients and independent finger extension was M4+ in seven and M4-in two patients. However, a patient who presented late at 8 mo had poorer finger outcomes with extension at M2-. All patients had independent movement of fingers. ConclusionsNerve transfer is a reliable method of post traumatic nerve repair and reinnervation, particularly in lower-middle income countries, even in cases where the nerve damage is severe and extensive and up to 6 mo may have elapsed between injury and presentation. Timely median to radial nerve transfer is a highly recommended option for radial nerve palsy, with regular follow-ups and physical therapy added to ensure positive outcomes.

Ultrasound therapy for a week promotes regeneration and reduces pro-inflammatory macrophages in a rat sciatic nerve autograft model

Peripheral nerve injury causes long-term motor dysfunction. Ultrasound (US) therapy is expected to accelerate peripheral nerve regeneration. However, its optimal usage and effects on macrophage phenotypes during peripheral nerve regeneration remain unknown. In this study, we investigated the optimal duration of US therapy and its effects on macrophage phenotype. Twenty-seven rats with autologous sciatic nerve grafting were divided into three groups: two received US therapy (1 MHz frequency, intensity of 140 mW/cm2, 20% duty cycle, 5 min/day) for one (US1) or 4 weeks (US4), and one group received sham stimulation. Immunohistochemistry was performed 3 and 7 days after injury in another set of 12 rats. Eight weeks after the injury, the compound muscle action potential amplitude of the gastrocnemius in the US1 and US4 groups was significantly higher than that in the sham group. The toe-spreading test showed functional recovery, whereas the gait pattern during treadmill walking did not recover. There were no significant differences in motor function, histomorphometry, or muscle weight between groups. Immunohistochemistry showed that US therapy decreased the number of pro-inflammatory macrophages seven days after injury. Therefore, US therapy for both one or 4 weeks can similarly promote reinnervation and reduce proinflammatory macrophages in autograft model rats.

Subcutaneous Dorsomedial Triangle of Forearm: Surgical Anatomy and Clinical Implication.

Background The purpose of the study was to provide a practical landmark for localizing the dorsal branch of the ulnar artery and nerve, to approach for microsurgical flaps, for harvesting nerve grafts and also to avoid these nerves during insertion of wrist arthroscopy portals. Material and methods Forty adult cadaveric upper limbs (20 right and 20 left) were dissected for localizing the dorsal branches of the ulnar artery and nerve. The ramification patterns of the nerve were mapped. The wrist arthroscopy portals are located radial and ulnar to the tendon of extensor carpi ulnaris at the level of the wrist joint, and their designated names are '6R & 6U', respectively. The distance of branches of the nerve from the 6U and 6R portals for wrist arthroscopy was recorded. Results The present study has delineated asubcutaneous dorsomedial triangular area in the distal forearm. The construction of this triangle uses palpable landmarks, i.e. pisiform bone, styloid process and subcutaneous border of the ulna. The measure of the sides of the triangle uses proportion rather than absolute measurements and hence is person specific. The dorsal branches of the ulnar nerve and artery are consistently given off in the triangle's upper third and middle third, respectively. Four branching patterns have been mapped, with one dominant pattern in 67.5% of limbs. In three-fourths of cases, one branch of the dorsal branch of the ulnar nerve consistently overlies the 6U portal and hence runs a higher risk of injury. Conclusion The study suggests more practical, accurate, reliable and consistent surface landmarks for the localization of the dorsal branch of the ulnar artery and nerve for reconstructive microsurgery for distal hand defects.

Histomorphometry of the Sural Nerve for Use as a CFNG in Facial Reanimation Procedures.

Facial palsy (FP) is a debilitating nerve pathology. Cross Face Nerve Grafting (CFNG) describes a surgical technique that uses nerve grafts to reanimate the paralyzed face. The sural nerve has been shown to be a reliable nerve graft with little donor side morbidity. Therefore, we aimed to investigate the microanatomy of the sural nerve. Biopsies were obtained from 15 FP patients who underwent CFNG using sural nerve grafts. Histological cross-sections were fixated, stained with PPD, and digitized. Histomorphometry and a validated software-based axon quantification were conducted. The median age of the operated patients was 37 years (5-62 years). There was a significant difference in axonal capacity decrease towards the periphery when comparing proximal vs. distal biopsies (p = 0.047), while the side of nerve harvest showed no significant differences in nerve caliber (proximal p = 0.253, distal p = 0.506) and axonal capacity for proximal and distal biopsies (proximal p = 0.414, distal p = 0.922). Age did not correlate with axonal capacity (proximal: R = -0.201, p = 0.603; distal: R = 0.317, p = 0.292). These novel insights into the microanatomy of the sural nerve may help refine CFNG techniques and individualize FP patient treatment plans, ultimately improving overall patient outcomes.

Facial Reanimation After Peripheral Facial Nerve Paralysis: A Single-institution Surgical Experience.

Facial nerve trauma occasionally develops during oral and maxillofacial surgery. This study was aimed at enhancing the available knowledge on facial nerve reanimation correlated to surgery and proposing our surgical algorithm. We retrospectively analyzed medical records of patients who underwent facial reanimation surgery at our hospital. The inclusion criterion was surgery for facial reanimation from January 2004 to June 2021. We included 383 eligible patients who underwent facial reanimation surgery. Trauma or maxillofacial neoplasms were noted in 208 of 383 and 164 of 383 cases, respectively. In 238 of 383 cases, nerve branches were likely more vulnerable. Facial nerve anastomosis was performed in 256 patients. Sixty-eight patients received nerve grafts. In 22 patients, distal facial nerve transfer to the masseteric nerve, sublingual nerve, or contralateral facial nerve was performed. Twenty-five patients received static surgery; in most cases, the temporalis fascia flap (20/25) was used. The nerve function outcomes were HB grade I (n=17), Grade Ⅱ (n=108), Grade Ⅲ (n=118), Grade Ⅳ (n=94), and Grade V (n=46). The mean follow-up time was 4.88 ± 3.93 years. Facial paralysis caused by trauma ( P =0.000), branch injury ( P =0.000), and the primary reconstruction of facial nerve ( P =0.000) were predictive of favorable treatment outcomes. Although facial nerve injury caused by trauma was more likely, cases of interference in facial expression could be limited, and so did the injury to branches. Nerve anastomosis was prioritized if a tension-free suture was possible. Maintaining the integrity of the nerve and shortening the duration of mimetic muscular denervation were crucial.

Supercharge End-to-Side Motor Transfer to a Long Nerve Graft to Enhance Motor Regeneration: An Experimental Rat Study.

Long nerve grafts are prone to chronic denervation, often resulting in unsatisfactory clinical outcomes. The authors aim to investigate whether supercharge end-to-side (SETS) motor nerve transfers to a long nerve graft can potentially enhance nerve regeneration and functional outcomes. A reversed long nerve graft was interposed between the C6 and the musculocutaneous nerve in 48 rats. The motor nerves near the C6 proximally and the musculocutaneous nerve distally were chosen for SETS transfer to the long nerve graft. There were four groups: (A) nerve graft only, (B) proximal SETS transfer, (C) distal SETS transfer, and (D) proximal and distal double SETS transfers. A grooming test was assessed at 4, 8, 12, and 16 weeks postoperatively. Biceps weight, compound muscle action potential amplitude, tetanic contraction force, and histomorphometric analysis of the musculocutaneous nerve were evaluated at 16 weeks. Long nerve grafts that received SETS transfers (groups B, C, and D) showed superior results compared with the control group. Proximal SETS transfer had significantly better outcomes than distal SETS transfer in electrodiagnostic parameters, whereas double SETS transfer had the highest axonal count and biceps compound muscle action potential amplitude. SETS motor transfers to long nerve grafts can effectively improve functional outcome and optimize nerve graft regeneration to the target nerve. Long nerve grafts yield suboptimal functional results. The experimental study showed that SETS motor transfer to a long nerve graft improves muscle functional outcomes. A double motor SETS transfer provides the best results. Proximal SETS transfer might have more benefits over distal transfer.

Facial Nerve High-Resolution Microanatomy Analysis of the Distal Intratemporal to Extracranial Pes Segment: Reconstructive Implications.

Current knowledge of facial nerve topography between the stylomastoid foramen to the pes anserinus is very limited. Elucidating this segment's intraneural microanatomy may be advantageous in certain clinical settings: the planning of nerve grafts for gaps extending from the proximal facial nerve trunk to distal branches or in determining coaptation sites for hypoglossal jump grafts to provide selective upper and lower facial tone. This study is the first to provide high-definition intraneural topography of the aforementioned segment to optimize reconstructive outcomes. Sixteen facial nerves extending from the second genu to the pes anserinus were harvested from eight cadavers en bloc to preserve orientation. Specimens were imaged by micro-computed tomography using a serial 6-μm protocol and digitally reconstructed three-dimensionally to be analyzed using bioinformatic tools. No clinically significant fascicular separation was noted between 14.4 mm proximal to the stylomastoid foramen until 4.4 mm distal to the foramen. Fascicles remained separate throughout the remainder of the specimen and were found to undergo a mean rotation of 45.5 degrees ( P = 0.0002) between 8.9 and 13.7 mm distal to the stylomastoid foramen. This reliable clockwise rotation in left nerves and counterclockwise rotation in right nerves resulted in superficially oriented fascicles entering the upper division of the pes anserinus, whereas deep-oriented fascicles entered the lower division. Intraneural facial nerve topography and rotation are consistent from 4 to 14 mm distal to the stylomastoid foramen, enabling surgeons to accurately place grafts targeted to either the upper or lower face, thus optimizing functional accuracy and minimizing synkinesis.

Functional Outcome of Dual Reinnervation with Cross-Facial Nerve Graft and Masseteric Nerve Transfer for Facial Paralysis.

The combination of cross-facial nerve graft (CFNG) and masseteric nerve transfer (MNT) for reinnervation of facial paralysis may provide advantages of both neural sources. However, quantitative functional outcome reports with a larger number of patients are lacking in the literature. Here, the authors describe their 8-year experience with this surgical technique. Twenty patients who presented with complete facial paralysis (duration, <12 months) received dual reinnervation with CFNG and MNT. The functional outcome of the procedure was evaluated with the physician-graded outcome metric eFACE scale. The objective artificial intelligence-driven software Emotrics and FaceReader were used for oral commissure measurements and emotional expression assessment, respectively. The mean follow-up was 31.75 ± 23.32 months. In the eFACE score, the nasolabial fold depth and oral commissure at rest improved significantly ( P < 0.05) toward a more balanced state after surgery. Postoperatively, there was a significant decrease in oral commissure asymmetry while smiling (from 19.22 ± 6.1 mm to 12.19 ± 7.52 mm). For emotional expression, the median intensity score of happiness, as measured by the FaceReader software, increased significantly while smiling (0.28; interquartile range, 0.13 to 0.64). In five patients (25%), a secondary static midface suspension with fascia lata strip had to be performed because of unsatisfactory resting symmetry. Older patients and patients with greater preoperative resting asymmetry were more likely to receive static midface suspension. The authors' results suggest that the combination of MNT and CFNG for reinnervation of facial paralysis provides good voluntary motion and may lessen the use of static midface suspension in the majority of patients. Therapeutic, IV.

Thermoelectric Freeze-Casting of Biopolymer Blends: Fabrication and Characterization of Large-Size Scaffolds for Nerve Tissue Engineering Applications.

Peripheral nerve injuries (PNIs) are detrimental to the quality of life of affected individuals. Patients are often left with life-long ailments that affect them physically and psychologically. Autologous nerve transplant is still the gold standard treatment for PNIs despite limited donor site and partial recovery of nerve functions. Nerve guidance conduits are used as a nerve graft substitute and are efficient for the repair of small nerve gaps but require further improvement for repairs exceeding 30 mm. Freeze-casting is an interesting fabrication method for the conception of scaffolds meant for nerve tissue engineering since the microstructure obtained comprises highly aligned micro-channels. The present work focuses on the fabrication and characterization of large scaffolds (35 mm length, 5 mm diameter) made of collagen/chitosan blends by freeze-casting via thermoelectric effect instead of traditional freezing solvents. As a freeze-casting microstructure reference, scaffolds made from pure collagen were used for comparison. Scaffolds were covalently crosslinked for better performance under load and laminins were further added to enhance cell interactions. Microstructural features of lamellar pores display an average aspect ratio of 0.67 ± 0.2 for all compositions. Longitudinally aligned micro-channels are reported as well as enhanced mechanical properties in traction under physiological-like conditions (37 °C, pH = 7.4) resulting from crosslinking treatment. Cell viability assays using a rat Schwann cell line derived from sciatic nerve (S16) indicate that scaffold cytocompatibility is similar between scaffolds made from collagen only and scaffolds made from collagen/chitosan blend with high collagen content. These results confirm that freeze-casting via thermoelectric effect is a reliable manufacturing strategy for the fabrication of biopolymer scaffolds for future peripheral nerve repair applications.

Decellularized Graft for Repairing Severe Peripheral Nerve Injuries in Sheep.

Peripheral nerve injuries resulting in a nerve defect require surgical repair. The gold standard of autograft (AG) has several limitations, and therefore, new alternatives must be developed. The main objective of this study was to assess nerve regeneration through a long gap nerve injury (50 mm) in the peroneal nerve of sheep with a decellularized nerve allograft (DCA). A 5-cm long nerve gap was made in the peroneal nerve of sheep and repaired using an AG or using a DCA. Functional tests were performed once a month and electrophysiology and echography evaluations at 6.5 and 9 months postsurgery. Nerve grafts were harvested at 9 months for immunohistochemical and morphological analyses. The decellularization protocol completely eliminated the cells while preserving the extracellular matrix of the nerve. No significant differences were observed in functional tests of locomotion and pain response. Reinnervation of the tibialis anterior muscles occurred in all animals, with some delay in the DCA group compared with the AG group. Histology showed a preserved fascicular structure in both AG and DCA; however, the number of axons distal to the nerve graft was higher in AG than in DCA. The decellularized graft assayed supported effective axonal regeneration when used to repair a 5-cm long gap in the sheep. As expected, a delay in functional recovery was observed compared with the AG because of the lack of Schwann cells.

Advances in Large Gap Peripheral Nerve Injury Repair and Regeneration with Bridging Nerve Guidance Conduits.

Peripheral nerve injury is a common complication of accidents and diseases. The traditional autologous nerve graft approach remains the gold standard for the treatment of nerve injuries. While sources of autologous nerve grafts are very limited and difficult to obtain. Nerve guidance conduits have been widely used in the treatment of peripheral nerve injuries as an alternative to nerve autografts and allografts. However, the development of nerve conduits does not meet the needs of large gap peripheral nerve injury. Functional nerve conduits can provide a good microenvironment for axon elongation and myelin regeneration. In this review, we summarize the manufacturing methods and different design types of functional bridging nerve conduits for nerve conduits combined with electrical or magnetic stimulation and loaded with Schwann cells, etc. It summarizes the literature and finds that the technical solutions of functional nerve conduits with electrical stimulation, magnetic stimulation and nerve conduits combined with Schwann cells can be used as effective strategies for bridging large gap nerve injury and provide an effective way for the study of large gap nerve injury repair. In addition, functional nerve conduits provide a new way to construct delivery systems for drugs and growth factors in vivo. This article is protected by copyright. All rights reserved.

The Evolution of the Reconstructive Strategy for Elbow Flexion for Acute C5, C6 Brachial Plexus Injuries over Two Decades.

Over the course of the past two decades, improved outcomes following brachial plexus reconstruction have been attributed to newer nerve transfer techniques. However, key factors aside from surgical techniques have brought improved consistency to elbow flexion techniques in the latter decade. One-hundred seventeen patients who underwent brachial plexus reconstruction from 1996 to 2006 were compared with 120 patients from 2007 to 2017. All patients were evaluated preoperatively and postoperatively to assess the recovery time and of elbow flexion strength. In the first decade, nerve reconstruction methods included proximal nerve grafting, intercostal nerve transfer, and Oberlin-I transfer. In the second decade, newer methods such as double fascicular transfer and ipsilateral C7 division transfer to the anterior division of upper trunk were introduced. About 78.6% of the first decade group versus 87.5% of the second decade group were able to reach M3 flexion strength (p = 0.04), with shorter time recovery to reach M3 in the 2nd decade. About 59.8% of the first decade group versus 65.0% of the second decade group were able to reach M4 (p = 0.28), but no significant difference in time of recovery. In both groups, the double fascicular nerve transfer had the highest impact when introduced in the second decade. More precise magnetic resonance imaging (MRI) techniques helped to diagnose the level of injury, the roots involved and evaluate the health of the donor nerves in preparation for intraplexus transfer. In addition to modified techniques in nerve transfers, (1) MRI-assisted evaluation and surgical exploration of the roots with (2) more judicious choice of donor nerves for primary nerve transfer were factors that ensured reliable and outcomes in the second decade.

Differential diagnosis and surgical management in chondrosarcoma of the jugular foramen

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.

Deferoxamine Promotes Peripheral Nerve Regeneration by Enhancing Schwann Cell Function and Promoting Axon Regeneration of Dorsal Root Ganglion

Deferoxamine (DFO) is a potent iron chelator for clinical treatment of various diseases. Recent studies have also shown its potential to promote vascular regeneration during peripheral nerve regeneration. However, the effect of DFO on the Schwann cell function and axon regeneration remains unclear. In this study, we investigated the effects of different concentrations of DFO on Schwann cell viability, proliferation, migration, expression of key functional genes, and axon regeneration of dorsal root ganglia (DRG) through a series of in vitro experiments. We found that DFO improves Schwann cell viability, proliferation, and migration in the early stages, with an optimal concentration of 25 μM. DFO also upregulates the expression of myelin-related genes and nerve growth-promoting factors in Schwann cells, while inhibiting the expression of Schwann cell dedifferentiation genes. Moreover, the appropriate concentration of DFO promotes axon regeneration in DRG. Our findings demonstrate that DFO, with suitable concentration and duration of action, can positively affect multiple stages of peripheral nerve regeneration, thereby improving the effectiveness of nerve injury repair. This study also enriches the theory of DFO promoting peripheral nerve regeneration and provides a basis for the design of sustained-release DFO nerve grafts.

Engineered hydrogels for peripheral nerve repair.

Peripheral nerve injury (PNI) is a complex disease that often appears in young adults. It is characterized by a high incidence, limited treatment options, and poor clinical outcomes. This disease not only causes dysfunction and psychological disorders in patients but also brings a heavy burden to the society. Currently, autologous nerve grafting is the gold standard in clinical treatment, but complications, such as the limited source of donor tissue and scar tissue formation, often further limit the therapeutic effect. Recently, a growing number of studies have used tissue-engineered materials to create a natural microenvironment similar to the nervous system and thus promote the regeneration of neural tissue and the recovery of impaired neural function with promising results. Hydrogels are often used as materials for the culture and differentiation of neurogenic cells due to their unique physical and chemical properties. Hydrogels can provide three-dimensional hydration networks that can be integrated into a variety of sizes and shapes to suit the morphology of neural tissues. In this review, we discuss the recent advances of engineered hydrogels for peripheral nerve repair and analyze the role of several different therapeutic strategies of hydrogels in PNI through the application characteristics of hydrogels in nerve tissue engineering (NTE). Furthermore, the prospects and challenges of the application of hydrogels in the treatment of PNI are also discussed.

Physical processing for decellularized nerve xenograft in peripheral nerve regeneration.

In severe or complex cases of peripheral nerve injuries, autologous nerve grafts are the gold standard yielding promising results, but limited availability and donor site morbidity are some of its disadvantages. Although biological or synthetic substitutes are commonly used, clinical outcomes are inconsistent. Biomimetic alternatives derived from allogenic or xenogenic sources offer an attractive off-the-shelf supply, and the key to successful peripheral nerve regeneration focuses on an effective decellularization process. In addition to chemical and enzymatic decellularization protocols, physical processes might offer identical efficiency. In this comprehensive minireview, we summarize recent advances in the physical methods for decellularized nerve xenograft, focusing on the effects of cellular debris clearance and stability of the native architecture of a xenograft. Furthermore, we compare and summarize the advantages and disadvantages, indicating the future challenges and opportunities in developing multidisciplinary processes for decellularized nerve xenograft.

Electroconductive poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticle-loaded silk fibroin biocomposite conduits for peripheral nerve regeneration

Peripheral nerve injury (PNI) often clinically relies on the use of nerve grafts taken from the patient to establish a therapeutic effect, though secondary site of injury and morbidity have prompted the medical community to find alternative solutions. A new trend in the development of biomaterials arises in the form of electro-conductive biomaterials, especially for electrically active tissues such as the peripheral nerves. In this work, novel poly(3,4-ethylenedioxythiophene) PEDOT nanoparticles (PEDOT NPs) were synthetized via the mini-emulsion method and were combined with silk fibroin (SF) to create conduits for PNI repair. The synthesized PEDOT NPs-loaded SF conduits showed optimal properties for peripheral nerve substitution from the physico-chemical and biological point of view. They displayed excellent mechanical and conductivity performance with the tensile moduli reaching 6.61 ± 0.55 MPa and the conduits reaching 5.4 · 10–4 S cm−1, respectively. The conduits did not possess apatite-forming capacity, which were resistant to bending occlusions for angles up to 50° and to suturing. The developed conduits are promising as a novel biomaterial for applications in peripheral nerve regeneration; in vitro experiments showed that they did not allow BJ fibroblast infiltration, avoiding scar tissue formation in the lumen, and they did not show any toxic effect for Schwann cells.

Sural communicating nerve for application as a vascularized nerve graft: A microneurovascular anatomic study in cadavers.

Sural nerve harvest causes paraesthesia to the lateral heel of the foot, which can debilitate those with already compromised proprioception. To circumvent this, we investigated an alternative donor nerve, branch of the lateral sural nerve complex called the sural communicating nerve (SCoNe), for its harvest and use as a vascularized nerve graft, in cadaver. The SCoNe was visualized by dissection in 15 legs from 8 human cadavers and the relationship of the SCoNe to the overall sural nerve complex was documented. The surface markings, dimensions, and the micro-neurovascular anatomy in the super-microsurgery range (up to 0.30 mm) of the SCoNe was recorded and analyzed. SCoNe graft surface marking was confined within a triangle drawn between the fibular head laterally, the popliteal vertical midline medially and the tip of the lateral malleolus inferiorly. The proximal end of the SCoNe was situated at a mean intersection distance of 5 cm from both the fibular head and popliteal midline respectively. The mean length of the SCoNe was 226 ± 43 mm with a mean proximal diameter of 0.82 mm and mean distal diameter of 0.93 mm. In 53% of the cadavers, an arterial input was present in the proximal third of the SCoNe and veins were predominantly (87%) present in the distal third. In 46% and 20% of the 15 legs respectively, there was a nutrient artery and vein perfusing the SCoNe in its central segment. The external mean diameter of this artery was 0.60 ± 0.30 mm, while the vein was slightly larger with a mean diameter of 0.90 ± 0.50 mm. SCoNe graft may preserve lateral heel sensation, compared to sural nerve harvest, pending clinical studies. It may have wide applications as a vascularized nerve graft, including being ideal as a vascularized cross-facial nerve graft because its nerve diameter is similar to the distal facial nerve branches. The accompanying artery is a good anastomotic match to the superior labial artery.