Polyglycolic Acid-collagen Tube Research Articles

TrkA inhibitor promotes motor functional regeneration of recurrent laryngeal nerve by suppression of sensory nerve regeneration

Recurrent laryngeal nerve (RLN) injury, in which hoarseness and dysphagia arise as a result of impaired vocal fold movement, is a serious complication. Misdirected regeneration is an issue for functional regeneration. In this study, we demonstrated the effect of TrkA inhibitors, which blocks the NGF-TrkA pathway that acts on the sensory/automatic nerves thus preventing misdirected regeneration among motor and sensory nerves, and thereby promoting the regeneration of motor neurons to achieve functional recovery. RLN axotomy rat models were used in this study, in which cut ends of the nerve were bridged with polyglycolic acid-collagen tube with and without TrkA inhibitor (TrkAi) infiltration. Our study revealed significant improvement in motor nerve fiber regeneration and function, in assessment of vocal fold movement, myelinated nerve regeneration, compound muscle action potential, and prevention of laryngeal muscle atrophy. Retrograde labeling demonstrated fewer labeled neurons in the vagus ganglion, which confirmed reduced misdirected regeneration among motor and sensory fibers, and a change in distribution of the labeled neurons in the nucleus ambiguus. Our study demonstrated that TrkAi have a strong potential for clinical application in the treatment of RLN injury.

Differentiated adipose-derived stem cells promote peripheral nerve regeneration.

Many reports have indicated that adipose-derived stem cells (ADSCs) are effective for nerve regeneration. We investigated nerve regeneration by combining a polyglycolic acid collagen (PGA-c) tube, which is approved for clinical use, and Schwann cell-like differentiated ADSCs (dADSCs). Fifteen-millimeter-long gaps in the sciatic nerve of rats were bridged in each group using tubes (group I), with tubes injected with dADSCs (group II), or by resected nerve (group III). Axonal outgrowth was greater in group II than in group I. Tibialis anterior muscle weight revealed recovery only in group III. Latency in nerve conduction studies was equivalent in group II and III, but action potential was lower in group II. Transplanted dADSCs maintained Schwann cell marker expression. ATF3 expression level in the dorsal root ganglia was equivalent in groups II and III. dADSCs maintained their differentiated state in the tubes and are believed to have contributed to nerve regeneration.

Clinical outcome and ultrasonographic evaluation of treatment using polyglycolic acid-collagen tube for chronic neuropathic pain after peripheral nerve injury

BackgroundA novel polyglycolic acid (PGA)-collagen tube has been available in Japan since March 2013, and the development of high-resolution ultrasonography has recently allowed detailed evaluation of nerves. The purpose of this study was to report the clinical outcomes and evaluations of in-vivo changes under high-resolution ultrasonography for treatment using PGA-collagen tube for painful chronic nerve injury. MethodsFour patients underwent surgical management of peripheral nerve neuroma, with nerve defects after neuroma resection reconstructed using PGA-collagen tube. Mean duration of follow-up was 30 months. Patients were surveyed to determine visual analog scale scores for pain before surgery and at final follow-up. At final follow-up, sensory function was evaluated using the Semmes–Weinstein test, static 2-point discrimination (2PD), and moving 2PD. Furthermore, we performed ultrasonography for all patients every 1 month after surgery. ResultsIn all cases, resting pain, radicular pain, and dysesthesia were improved immediately after the operation and remained improved until the last follow-up. At the time of final follow-up, the Semmes–Weinstein test was red in 2 cases and blue in 2 cases. Mean static 2PD was 15.5 ± 5.3 mm and mean moving 2PD was 11.5 ± 5.3 mm. Ultrasonography revealed that the PGA outer wall had disappeared by 3 months postoperatively, and a hypoechoic linear shadow bridged the proximal and distal stumps. Swelling of the junction between nerve and nerve conduits was revealed at 4 months after surgery and remained until last follow-up. ConclusionsAll patients were very satisfied with pain relief, but recovery of sensory function was insufficient. Ultrasonographic evaluation after using PGA-collagen tube for painful chronic peripheral nerve injury was useful for observing in-vivo changes. Type of study/level of evidenceTherapeutic IV.

Ethanol-Induced Cervical Sympathetic Ganglion Block Applications for Promoting Canine Inferior Alveolar Nerve Regeneration Using an Artificial Nerve.

Polyglycolic acid collagen (PGA-C) tubes are bio-absorbable nerve tubes filled with collagen of multi-chamber structure, which consist of thin collagen films. Favorable clinical outcomes have been achieved when using these tubes for the treatment of damaged inferior alveolar nerve (IAN). A critical factor for the successful nerve regeneration using PGA-C tubes is blood supply to the surrounding tissue. Cervical sympathetic ganglion block (CSGB) creates a sympathetic blockade in the head and neck region thus increasing blood flow in the area. To ensure an adequate effect, the blockade must be administered with local anesthetics one to two times a day for several consecutive weeks; this poses a challenge when creating animal models for investigating this technique. To address this limitation, we developed an ethanol-induced CSGB in a canine model of long-term increase in blood flow in the orofacial region. We examined whether IAN regeneration via PGA-C tube implantation can be enhanced by this model. Fourteen Beagles were each implanted with a PGA-C tube across a 10-mm gap in the left IAN. The IAN is located within the mandibular canal surrounded by bone, therefore we chose piezoelectric surgery, consisting of ultrasonic waves, for bone processing, in order to minimize the risk of nerve and vessel injury. A good surgical outcome was obtained with this approach. A week after surgery, seven of these dogs were subjected to left CSGB by injection of ethanol. Ethanol-induced CSGB resulted in improved nerve regeneration, suggesting that the increased blood flow effectively promotes nerve regeneration in IAN defects. This canine model can contribute to further research on the long-term effects of CSGB.

Evaluation of the effects of a polyglycolic acid-collagen tube in the regeneration of facial nerve defects in rats.

The purpose of this study was to assess the utility of a polyglycolic acid-collagen tube and to investigate its possible application in the field of facial nerve reconstruction. Wistar rats were used in this study. In the operation, a periauricular incision was made to expose the buccal and marginal branches of the facial nerve. Gaps of 10 mm were created by resection of a part of the nerve into the marginal branches and the buccal branch of the left facial nerve. The left marginal branch gap was bridged with a 10-mm polyglycolic acid-collagen tube or an autograft. At 12 weeks after the operation, nerve regeneration was assessed based on clinical, histopathological, and electrophysiological evaluations. The functional recovery of the vibrissal muscle was observed with the polyglycolic acid-collagen tube. However, the functional recovery obtained with the use of the polyglycolic acid-collagen tube was inferior to that obtained with an autograft. We found that polyglycolic acid-collagen tubes could be applied in facial nerve gap reconstruction. However, further improvements will be necessary to achieve results that are equivalent to those obtained with autografts.

MP84-03 INTERPOSITION OF NOVEL NERVE-REGENERATION CONDUIT AFTER WIDE EXCISION OF THE NEUROVASCULAR BUNDLE DURING RADICAL PROSTATECTOMY DID NOT IMPROVE POSTOPERATIVE ERECTILE FUNCTION

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease II1 Apr 2018MP84-03 INTERPOSITION OF NOVEL NERVE-REGENERATION CONDUIT AFTER WIDE EXCISION OF THE NEUROVASCULAR BUNDLE DURING RADICAL PROSTATECTOMY DID NOT IMPROVE POSTOPERATIVE ERECTILE FUNCTION Nobuyuki Hinata, Junya Furukawa, Ken-ichi Harada, Yuzo Nakano, and Masato Fujisawa Nobuyuki HinataNobuyuki Hinata More articles by this author , Junya FurukawaJunya Furukawa More articles by this author , Ken-ichi HaradaKen-ichi Harada More articles by this author , Yuzo NakanoYuzo Nakano More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2771AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In select cases of high-volume prostate cancer, a wide excision of the neurovascular bundle is the treatment option. However, this technique could cause postoperative erectile dysfunction. Treatment using nerve-regeneration conduit (NRC) has been shown to be equally or more effective than the nerve autograft and nerve suture for patients with somatic nerve injuries. We investigated efficacy of NRC interposition on return of erectile function after wide excision during radical prostatectomy. METHODS After institutional review board approval, a total of 78 patients (42 unilateral, 36 bilateral) underwent unilateral or bilateral wide excision during robot-assisted radical prostatectomy between December 2013 and September 2016. They were classified into 2 groups, that is unilateral nerve preservation with contralateral NRC (polyglycolic acid collagen tube; NerbridgeTM) interposition and bilateral wide excision with bilateral NRC interposition. Postoperative data of these patients were compared with the data obtained from 136 patients who underwent wide excision during RARP between October 2010 to November 2013. Potency was estimated by the SHIM score and erection hardness score (EHS). The data from the patients with preoperative SHIM score > 17 were used for the analyses. RESULTS No complication related to the interposition of the NRC was observed. Recovery rates of the SHIM score to the baseline at 12 months postoperatively for unilateral and bilateral groups were 15.8% and 0%, respectively. The recovery of EHS scores to the baseline were not observed at 12 months postoperatively in both groups. The recovery rate of EHS score with NRC interposition group was not significantly higher than the rate without NRC interposition group for both of the unilateral and bilateral groups. CONCLUSIONS NRC interposition did not improve postoperative erectile function in patients who received wide excision during RARP. Scaffold for peripheral autonomic nerve regeneration seemed not to work because mesh-like cavernous nerves could not be replaced by a linear nerve. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1125 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Nobuyuki Hinata More articles by this author Junya Furukawa More articles by this author Ken-ichi Harada More articles by this author Yuzo Nakano More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Can nerve regeneration on an artificial nerve conduit be enhanced by ethanol-induced cervical sympathetic ganglion block?

This study aimed to determine whether nerve regeneration by means of an artificial nerve conduit is promoted by ethanol-induced cervical sympathetic ganglion block (CSGB) in a canine model. This study involved two experiments—in part I, the authors examined the effect of CSGB by ethanol injection on long-term blood flow to the orofacial region; part II involved evaluation of the effect of CSGB by ethanol injection on inferior alveolar nerve (IAN) repair using polyglycolic acid-collagen tubes. In part I, seven Beagles were administered left CSGB by injection of 99.5% ethanol under direct visualization by means of thoracotomy, and changes in oral mucosal blood flow in the mental region and nasal skin temperature were evaluated. The increase in blood flow on the left side lasted for 7 weeks, while the increase in average skin temperature lasted 10 weeks on the left side and 3 weeks on the right. In part II, fourteen Beagles were each implanted with a polyglycolic acid-collagen tube across a 10-mm gap in the left IAN. A week after surgery, seven of these dogs were administered CSGB by injection of ethanol. Electrophysiological findings at 3 months after surgery revealed significantly higher sensory nerve conduction velocity and recovery index (ratio of left and right IAN peak amplitudes) after nerve regeneration in the reconstruction+CSGB group than in the reconstruction-only group. Myelinated axons in the reconstruction+CSGB group were greater in diameter than those in the reconstruction-only group. Administration of CSGB with ethanol resulted in improved nerve regeneration in some IAN defects. However, CSGB has several physiological effects, one of which could possibly be the long-term increase in adjacent blood flow.

Artificial sensory organs: latest progress.

This study introduces the latest progress on the study of artificial sensory organs, with a special emphasis on the clinical results of artificial nerves and the concept of in situ tissue engineering. Peripheral nerves have a strong potential for regeneration. An artificial nerve uses this potential to recover a damaged peripheral nerve. The polyglycolic acid collagen tube (PGA-C tube) is a bio-absorbable tube stuffed with collagen of multi-chamber structure that consists of thin collagen films. The clinical application of the PGA-C tube began in 2002 in Japan. The number of PGA-C tubes used is now beyond 300, and satisfactory results have been reported on peripheral nerve repairs. This PGA-C tube is also effective for patients suffering from neuropathic pain.

Effect of cervical sympathetic ganglionectomy on facial nerve reconstruction using polyglycolic acid-collagen tubes

A polyglycolic acid-collagen (PGA-c) tube was used as an artificial nerve guide during facial nerve reconstruction performed in a canine model of stellate ganglion block (SGB). The model was generated using a cervical sympathetic ganglionectomy. We evaluated the effects of blood flow on nerve regeneration.First, we resected the left cervical sympathetic ganglion in beagles (n=6). We assessed buccal mucosal blood flow and nasal skin temperatures once per week for 12weeks and Horner’s sign 2, 4, and 6months after resection. We compared these values to those measured prior to resection. Blood flow was increased for 6–11weeks, but sympathetic control remained blocked after 6months.Second, we divided beagles into 3 groups: resection models (negative control), from which 7mm of the left facial nerve buccal branch was resected (n=5); reconstruction models, which underwent nerve reconstruction using PGA-c tubes (n=6); and SGB+reconstruction models, which underwent a left cervical sympathetic ganglionectomy immediately after reconstruction (n=6). The right side of the face served as control (n=17). Nerve regeneration was significantly greater in the SGB+reconstruction model dogs than in the reconstruction model dogs, as measured by both electrophysiological and morphological analyses at postoperative week 12. In particular, motor nerve conduction velocity was increased approximately 2-fold (p=0.018). We were able to generate an SGB model with long-term increased blood flow facilitated by the promotion of facial nerve regeneration by PGA-c tubes.

Prognosis After Surgical Treatment of Trigeminal Neuropathy with a PGA-c Tube: Report of 10 Cases.

Although surgery using a polyglycolic acid-collagen (PGA-c) tube is effective for peripheral nerve injury-induced chronic hand pain, it has not been applied to trigeminal nerve lesions because of the difficult approach. We used a PGA-c tube during surgery for trigeminal neuropathy and evaluated its prognosis based on the outcomes. Case report. In the dental anesthesia division of a university hospital, 11 patients with severe dysesthesia underwent surgical repair of a damaged lingual nerve (LN) or inferior alveolar nerve (IAN). One patient was lost to follow-up. Changes in quantitative sensory testing (QST) and the presence of dysesthesia as a treatment outcome were compared preoperatively and postoperatively in 10 patients. Two surgical treatments, bridging or encircling peripheral nerves, were applied. Bridging of both stumps was selected when neurotmesis was detected or the nerve was lacerated during surgery (N = 4). Otherwise, a longitudinal PGA-c tube was used to encircle the lesion (N = 6). Outcomes were evaluated 2 months to 8 years postoperatively. Both methods improved the patients' condition based on QST results (brush stroke perception, mechanical touch threshold, sensitivity to cold/hot stimuli). Preoperative allodynia or dysesthesia was resolved in six patients and greatly reduced in four. Two patients (one with inflammation-induced pain, one with implant-related pain) developed prolonged postoperative allodynia requiring pain-relief medication. Use of a PGA-c tube for surgical treatment of intractable pain due to LN or IAN neuropathy helps alleviate sensory impairment. The possibility of new dysesthesias emerging postoperatively, however, should be noted.

Experimental repair of phrenic nerve using a polyglycolic acid and collagen tube

The feasibility of a nerve guide tube for regeneration of the phrenic nerve with the aim of restoring diaphragmatic function was evaluated in a canine model. The nerve tube, made of woven polyglycolic acid mesh, had a diameter of 3 mm and was filled with collagen sponge. This polyglycolic acid-collagen tube was implanted into a 10-mm gap created by transection of the right phrenic nerve in 9 beagle dogs. The tubes were implanted without a tissue covering in 5 of the 9 dogs (group I), and the tubes were covered with a pedicled pericardial fat pad in 4 dogs (group II). Chest x-ray films, muscle action potentials, and histologic samples were examined 4 to 12 months after implantation. All of the dogs survived without any complications. x-ray film examination showed that the right diaphragm was paralyzed and elevated in all dogs until 3 months after implantation. At 4 months, movement of the diaphragm in the implanted side was observed during spontaneous breathing in 1 dog of group I and in 3 dogs of group II. In the dogs showing diaphragm movement, muscle action potentials were evoked in the diaphragm muscle, indicating restoration of nerve function. Regeneration of the phrenic nerve structure was also examined on the reconstructed site using electron microscopy. The polyglycolic acid-collagen tube induced functional recovery of the injured phrenic nerve and was aided by coverage with a pedicled pericardial fat pad.

Regeneration of Peripheral Nerve Gaps With a Polyglycolic Acid-Collagen Tube

Regeneration of Peripheral Nerve Gaps With a Polyglycolic Acid-Collagen Tube

Surgical relief of causalgia with an artificial nerve guide tube: Successful surgical treatment of causalgia (Complex Regional Pain Syndrome Type II) by in situ tissue engineering with a polyglycolic acid-collagen tube

Two patients with causalgia associated with allodynia and finger contracture were treated surgically with a bioresorbable nerve guide tube made from polygycolic acid and collagen: the injured segment of the digital nerve was resected and the resulting gap (25 and 36 mm) was bridged with the tube. In both cases, a neuroma was found on the injured nerve and many sprouting branches were. After reconstruction, the causalgia and allodynia disappeared and movement of the fingers recovered during the following 6 months. Functional recovery was objectively identified for 1 year and 9 months. Both patients regained full use of their finger and were free of discomfort for up to 24 and 18 months, respectively. Since the first description of causalgia in 1864, there has been no definitive treatment for this intractable burning pain. Our experience shows that at least some types of causalgia can be resolved successfully by surgery.

Experimental study on the regeneration of peripheral nerve gaps through a polyglycolic acid–collagen (PGA–collagen) tube

We have developed a bioabsorbable polyglycolic acid (PGA) tube filled with collagen sponge (PGA–collagen tube) as a nerve connective guide, and compared its effectiveness with that of autograft in terms of nerve regeneration across a gap. The PGA–collagen tube was implanted into 24 beagle dogs across a 15-mm gap in the left peroneal nerve. The right peroneal nerve was reconstructed with the autograft harvested from the left side, as a control. After the surgery, the connective tissue extended from both cut ends in the PGA–collagen tube and connected again at the center. Pathologically, the collagen sponge in the tube provided adequate scaffolding for nerve tissue extension, and the nerve tissue reconnected within 3 weeks. Electrophysiologically, muscle-evoked potentials (MEPs) and compound nerve action potentials (CNAPs) were detected 18 days after the surgery. For up to 6 months postsurgery, CNAPs and somatosensory-evoked potentials (SEPs) on the PGA–collagen side had a shorter latency and larger peak voltage than those on the autograft side. The myelinated axons on the PGA side were larger in diameter than those on the autograft side. It is suggested that the PGA–collagen tube has the potential to be an effective alternative to conventional autografting for the repair of some peripheral nerve defects.

Use of a newly developed artificial nerve conduit to assist peripheral nerve regeneration across a long gap in dogs.

There is now considerable evidence that peripheral nerves have the potential to regenerate if an appropriate microenvironment is provided. However, there are only a few reports of the successful use of artificial nerve conduits to repair major nerve defects more than 30 mm in length. In this study, we examined nerve regeneration across a long gap in the dog peroneal nerve using a novel artificial nerve conduit developed by our group. The conduit consists of a polyglycolic acid (PGA) collagen tube filled with laminin coated collagen fibers. In 12 dogs, the nerve conduit was implanted across an 80 mm gap in the left peroneal nerve. Three months after surgery, compound muscle action potentials (CMAPs) and somatosensory evoked potentials (SEPs) were detected. Evaluation of locomotor function revealed obvious limping for up to 3 months, but no marked difficulty in walking by 6 months. Microscopic observation of the regenerated nerve segment at 12 months showed numerous myelinated nerve fibers, which were smaller in diameter and enclosed in a thinner myelin sheath than normal axons. These results suggest that our artificial nerve conduit has potential usefulness in enhancing peripheral nerve regeneration, even across large gaps.

Nerve regeneration across a 25-mm gap bridged by a polyglycolic acid-collagen tube: a histological and electrophysiological evaluation of regenerated nerves

In the study reported here we have examined the nerve regeneration that occurs over a 25-mm gap using a novel biodegradable nerve guide tube. The tube was a composite of polyglycolic acid (PGA) mesh coated with collagen which was filled with neurotrophic factors. The left sciatic nerve of ten adult cats was dissected. The stumps were connected by the tube, and fixed gap. Histological examinations carried out 4–16 months after implantation of the tube revealed regeneration of well vascularized nerve tissue. Regeneration of both myelinated, unmyelinated axons and Schwann cells was confirmed by electron microscopy 5 months after surgery. Following injection of horseradish peroxidase (HRP) into a site peripheral to the regenerated segment of the sciatic nerves, motoneurons in the ventral horn of the spinal cord, afferent terminals in the medial portion of the dorsal column of the medulla oblongata, and sensory afferent nerve terminals in the dorsal horn of the spinal cord were labelled. Electrophysiological examinations revealed restoration of evoked electromyograms and sensory evoked potentials (SEPs) recorded from the cerebral cortex as well as the spinal cord. We also found that some of the regenerated motor axons exhibited branching in the regenerated segments. In two cases, a single motoneuronal axon from the regenerated side projected to both flexors and extensors, simultaneously. Our results indicate that the PGA-collagen composite tube is a promising tool for use as a nerve guide tube in peripheral nerve regeneration.