• Garcinia kola
• curcumin
• diabetes
• sciatic nerve
• stereology
• transection

• Animals
• Curcumin/pharmacology
• Curcumin/chemistry
• Sciatic Nerve/drug effects
• Sciatic Nerve/injuries
• Rats, Wistar
• Male
• Nerve Regeneration/drug effects
• Rats
• Diabetes Mellitus, Experimental/drug therapy
• Neuroprotective Agents/pharmacology
• Neuroprotective Agents/chemistry

• alginate
• hydrogel
• nerve
• orthopedic surgery
• repair

• Child
• Humans
• Hand Injuries/surgery
• Hand Injuries/diagnostic imaging
• Microsurgery

• nerve guide conduits
• nerve regeneration
• nerve repair
• peripheral nerve injury

• Humans
• Peripheral Nerve Injuries/therapy
• Peripheral Nerve Injuries/surgery
• Peripheral Nerve Injuries/physiopathology
• Nerve Regeneration/physiology
• Animals
• Guided Tissue Regeneration/methods

• Critical-sized nerve injury
• Drug-eluting conduit
• Large-gap sciatic nerve repair
• Peripheral nerve injury
• Tacrolimus

• Animals
• Tacrolimus/pharmacology
• Tacrolimus/administration & dosage
• Nerve Regeneration/drug effects
• Peripheral Nerve Injuries/drug therapy
• Peripheral Nerve Injuries/therapy
• Rats
• Sciatic Nerve/injuries
• Sciatic Nerve/drug effects
• Rats, Sprague-Dawley
• Polyesters/chemistry
• Disease Models, Animal
• Guided Tissue Regeneration/methods

• 1R41NS112066-01A1 NINDS NIH HHS
• 1R41NS112066-01A1 NINDS NIH HHS
• 1R41NS112066-01A1 NINDS NIH HHS
• 1R41NS112066-01A1 NINDS NIH HHS

• Clinical Translation
• Hair Keratin
• Hydrogel
• Regenerative Medicine
• Tissue Engineering

• neurology
• trauma

• Male
• Humans
• Female
• Hand
• Hypesthesia
• Neuroma/etiology
• Neuroma/surgery
• Pain/etiology
• Paresthesia

• Swedish Research Council
• Swedish Diabetes Foundation
• Region Skåne
• Skåne University Hospital
• Regional Agreement on Medical Training and Clinical Research (ALF) between Region Skåne and Lund University
• Regional Agreement on Medical Training and Clinical Research (ALF) between Region Östergötland and Linköping University
• Lund University

• Microsurgery
• Nerve conduit
• Posttraumatic peripheral nerve repair
• Umbilical artery

• Humans
• Rats
• Animals
• Umbilical Arteries
• Sciatic Nerve
• Nerve Regeneration
• Axons
• Autografts

• Tissue Bank of France (TBF)

• Health Commission of Jilin Province
• Fundamental Research Funds for the Central Universities
• Education Department of Jilin Province
• Jilin Scientific and Technological Development Program
• National Natural Science Foundation of China

Injuries of the bone/cartilage and central nervous system are still a serious socio-economic problem. They are an effect of diversified, difficult-to-access tissue structures as well as complex regeneration mechanisms. Currently, commercially available materials partially solve this problem, but they do not fulfill all of the bone/cartilage and neural tissue engineering requirements such as mechanical properties, biochemical cues or adequate biodegradation. There are still many things to do to provide complete restoration of injured tissues. Recent reports in bone/cartilage and neural tissue engineering give high hopes in designing scaffolds for complete tissue regeneration. This review thoroughly discusses the advantages and disadvantages of currently available commercial scaffolds and sheds new light on the designing of novel polymeric scaffolds composed of hydrogels, electrospun nanofibers, or hydrogels loaded with nano-additives.

• composites
• electrospun nanofibers
• hydrogels
• injectable materials
• nanoparticles
• polymers
• scaffolds
• tissue engineering

• biocompatibility
• foreign body reaction
• nerve neuroprosthetics
• neural implants
• neural interface
• peripheral nerve stimulation

• Wellcome Trust

Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system; meaningful recovery was defined as M3–M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restoration of shoulder abduction and elbow flexion. Thus, if direct coaptation is not possible, use of acellular nerve allografts is a suitable option. This study was approved by the Medical Ethical Committee of the First Affiliated Hospital of Sun Yat-sen University, China (Application ID: [2017] 290) on November 14, 2017.

• accessary nerve
• brachial plexus avulsion injury
• contralateral C7 nerve root transfer
• direct repair
• elbow function
• human acellular nerve allograft
• nerve graft
• nerve regeneration
• nerve transfer
• neural regeneration
• phrenic nerve
• shoulder function

• digital nerve manipulation
• soft pneumatic actuator
• surgical gripper

• R-397-000-204-133 National University of Singapore Young Investigator Award

When primary repair of transected peripheral nerves is not possible due to large gaps, nerve grafts or repair using conduits are other options to bridge the gap such that the nerve is repaired without tension. When nerve gaps are repaired primarily, there is a worry about tension, failure, and poor healing. In this biomechanical study comparing nerves repaired primarily versus those repaired with conduits, we hypothesized that conduit repair provided greater mechanical breaking strength.

We dissected fresh cadaveric sheep hooves and transacted their peripheral nerves. Subsequently, we divided these transacted nerves into 2 groups: primary repair versus repair using a nerve conduit. After repair using a standardized technique, we tensioned each of these repairs via a load tester and recorded the force required till repair failure occurred.

Six nerves using primary nerve repair and 6 nerves repaired with a nerve conduit (10 mm length × 2.5 mm diameter) were studied. The average breaking strength of the nerves repaired with the nerve conduit was 0.92 N and that using the primary nerve repair technique was 0.46 N (P = 0.001). All the nerves repaired using nerve conduit repair had an additional 5 mm added to their total length as compared with the nerves in the other group.

Nerve repair using a nerve conduit ensures a higher breaking strength and potentially a greater tension-free repair as compared with primary nerve repairs in a sheep model. This study supports the use of conduits in the bridging of nerve gaps.

• Tissue engineered nerve
• acellular xenogeneic nerve
• adipose-derived stem cells
• facial nerve repair
• platelet rich plasma
• rabbit

• Animals
• Biomimetic Materials/chemistry
• Biomimetic Materials/therapeutic use
• Biomimetics/methods
• Humans
• Nerve Regeneration
• Peripheral Nerve Injuries/physiopathology
• Peripheral Nerve Injuries/therapy
• Peripheral Nerves/physiology
• Tissue Engineering/methods
• Tissue Scaffolds/chemistry

• R01 HL118084 NHLBI NIH HHS

• Schwann cells
• cauda equina
• motor neurons
• regeneration
• retrograde labeling

• caprolactone
• clinical evaluation
• materials testing
• nerve conduit
• peripheral nerve injury
• postoperative period

• Actins/metabolism
• Allografts
• Animals
• Cell Nucleus/metabolism
• Electrophoresis, Polyacrylamide Gel
• Extracellular Matrix/metabolism
• Female
• Immunohistochemistry
• Mass Spectrometry
• Microscopy, Electron
• Molecular Weight
• Nerve Regeneration
• Neurons
• Peripheral Nervous System/physiology
• Pilot Projects
• Rats
• Rats, Sprague-Dawley
• Reproducibility of Results
• Sciatic Nerve/transplantation

• FK506
• GDNF
• NGF
• Neurite growth in vitro
• dosage
• nerve regeneration
• potentiation

Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration.

To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve repair using a type I collagen nerve conduit. Patients were re-examined at a minimal follow-up of 14.0 months and a mean follow-up of 19.9 months. Regeneration of nerve tissue within the conduits was assessed by nerve conduction velocity (NCV), a static two-point discrimination (S2PD) test, and as disability of arm shoulder and hand (DASH) outcome measure scoring. Quality of life measures including patients’ perceived satisfaction and residual pain were evaluated using a visual analog scale (VAS). No implant-related complications were observed. Seven out of 10 patients reported being free of pain, and the mean VAS was 1.1. The mean DASH score was 17.0. The S2PD was below 6 mm in 40%, between 6 and 10 mm in another 40% and above 10 mm in 20% of the patients. Eight out of 10 patients were satisfied with the procedure and would undergo surgery again. Early treatment correlated with lower DASH score levels. The use of type I collagen in large-diameter gaps in young patients and early treatment presented superior functional outcomes.

• Type I collagen nerve conduit
• biocompatibility
• peripheral nerve repair

Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery.

• Sunderland IV
• animal models
• longitudinal epineural incision
• nerve regeneration
• nerve regeneration and repair
• neural regenerati
• peripheral nerve
• rats
• sciatic nerve injury

• Animals
• Biocompatible Materials/therapeutic use
• Humans
• Spinal Cord Injuries/therapy
• Spinal Cord Regeneration

• bioactive proteins
• drug delivery
• electrospun fibers
• nerve conduit

Pretreatment of nerve allografts by exposure to irradiation or green tea polyphenols can eliminate neuroimmunogenicity, inhibit early immunological rejection, encourage nerve regeneration and functional recovery, improve tissue preservation, and minimize postoperative infection. In the present study, we investigate which intervention achieves better results. We produced a 1.0 cm sciatic nerve defect in rats, and divided the rats into four treatment groups: autograft, fresh nerve allograft, green tea polyphenol-pretreated (1 mg/mL, 4°C) nerve allograft, and irradiation-pretreated nerve allograft (26.39 Gy/min for 12 hours; total 19 kGy). The animals were observed, and sciatic nerve electrophysiology, histology, and transmission electron microscopy were carried out at 6 and 12 weeks after grafting. The circumference and structure of the transplanted nerve in rats that received autografts or green tea polyphenol-pretreated nerve allografts were similar to those of the host sciatic nerve. Compared with the groups that received fresh or irradiation-pretreated nerve allografts, motor nerve conduction velocity in the autograft and fresh nerve allograft groups was greater, more neurites grew into the allografts, Schwann cell proliferation was evident, and a large number of new blood vessels was observed; in addition, massive myelinated nerve fibers formed, and abundant microfilaments and microtubules were present in the axoplasm. Our findings indicate that nerve allografts pretreated by green tea polyphenols are equivalent to transplanting autologous nerves in the repair of sciatic nerve defects, and promote nerve regeneration. Pretreatment using green tea polyphenols is better than pretreatment with irradiation.

• allograft
• alternative
• green tea polyphenols
• irradiation
• nerual regeneration
• nerve defects
• nerve regeneration
• nerve repair
• peripheral nerve injury
• sciatic nerve
• transplantation

• biopolymers
• scaffolds
• regenerative medicine

• Animals
• Biopolymers
• Bone Regeneration
• Corneal Transplantation
• Heart/physiology
• Humans
• Muscle, Skeletal/physiology
• Nerve Regeneration
• Regenerative Medicine
• Tissue Scaffolds

• R01 DE017207 NIDCR NIH HHS
• R01 EY020856 NEI NIH HHS
• K12 GM074869 NIGMS NIH HHS
• R01 EB011620 NIBIB NIH HHS
• P41 EB002520 NIBIB NIH HHS

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair.

• Peripheral nerve injury
• Adipose derived stem cells
• Cell based therapies
• Stem cells

Peripheral nerve injury is a serious problem affecting significantly patients’ life. Autografts are the “gold standard” used to repair the injury gap, however, only 50% of patients fully recover from the trauma. Artificial conduits are a valid alternative to repairing peripheral nerve. They aim at confining the nerve environment throughout the regeneration process, and providing guidance to axon outgrowth. Biocompatible materials have been carefully designed to reduce inflammation and scar tissue formation, but modifications of the inner lumen are still required in order to optimise the scaffolds. Biomicking the native neural tissue with extracellular matrix fillers or coatings showed great promises in repairing longer gaps and extending cell survival. In addition, extracellular matrix molecules provide a platform to further bind growth factors that can be released in the system over time. Alternatively, conduit fillers can be used for cell transplantation at the injury site, reducing the lag time required for endogenous Schwann cells to proliferate and take part in the regeneration process. This review provides an overview on the importance of extracellular matrix molecules in peripheral nerve repair.

• extracellular matrix
• fillers
• growth factors
• nerve conduits
• peripheral nerve repair
• surface modification

Management of brachial plexus injury is a demanding field of hand and upper extremity surgery. With currently available microsurgical techniques, functional gains are rewarding in upper plexus injuries. However, treatment options in the management of flail and anaesthetic limb are still evolving. Last three decades have witnessed significant developments in the management of these injuries, which include a better understanding of the anatomy, advances in the diagnostic modalities, incorporation of intra-operative nerve stimulation techniques, more liberal use of nerve grafts in bridging nerve gaps, and the addition of new nerve transfers, which selectively neurotise the target muscles close to the motor end plates. Newer research works on the use of nerve allografts and immune modulators (FK 506) are under evaluation in further improving the results in nerve reconstruction. Direct reimplantation of avulsed spinal nerve roots into the spinal cord is another area of research in brachial plexus reconstruction.

• Brachial plexus injuries
• nerve grafts
• recent advances
• reimplantation of avulsed spinal nerve roots
• selective nerve transfers

• Cauda equina
• Conus medullaris
• Nerve root avulsion
• Neuroregeneration
• PLGA scaffold
• Spinal cord injury

• Electrospinning
• In vivo model
• Sciatic nerve regeneration
• Tubular conduit

• Acellular nerve allograft
• Nerve conduits
• Nerve repair

• Adipose-derived stem cells
• FDA-approved collagen conduits
• Peripheral nerve regeneration
• Schwann cell-like differentiation

• Adult Stem Cells/cytology
• Animals
• Cell Differentiation
• Collagen/chemistry
• Male
• Mesenchymal Stem Cells/cytology
• Nerve Regeneration
• Rats, Sprague-Dawley
• Schwann Cells/cytology
• Sciatic Nerve/injuries
• Sciatic Nerve/pathology
• Sciatic Nerve/physiopathology
• Tissue Engineering

• Collagen
• Collagène
• Conduit de régénération nerveuse
• Facial nerve
• Nerf facial
• Nerve gap
• Nerve regeneration conduit
• Neurotube
• Perte de substance nerveuse