Comparison of primary repair and repair with polyglycolic acid coated tube in recurrent laryngeal nerve cuts (an experimental study)

BackgroundRecurrent laryngeal nerve (RLN) injury is an important complication of thyroid surgery. In our study, we aimed to compare the effects of primary repair and polyglycolic acid (PGA) coated tube repair on nerve function and regeneration in RLN cuts in rats.MethodsTwenty seven rats were used for the study. Group-1 with only nerve cuts, group-2 with primary repair, and group-3 with conduit repair. The study was planned over two-stage surgery. In the first step, nerve defect formation and nerve repair were performed in the same session. In the second step, samples were taken from the subjects for histopathological.ResultsVocal cord mobility was proportionally higher in group-3 than other groups. However, there was no statistically significant difference between the groups (p < 0.239). The mean number of highest axons were detected the group-3.ConclusionsWe think that PGA coated conduit can provide a more accurate orientation of nerve fibers by creating an isolated environment when compared to the primary repair. And this may be the cause of functional improvement in the nerve.     

Infections in neurosurgery: A randomized comparison between silk and polyglycolic acid

Summary Silk or polyglycolic acid (PGA) was chosen at random for 1,011 patients operated on in the department during a 19 month period in 1981. There was no difference in the incidence of serious infections between the two groups. A significantly higher incidence of suture fistulas in the silk group indicates the use of PGA for buried sutures.     

Changes in type I, II, and X collagen immunoreactivity of the mandibular condylar cartilage in a naturally aging rat model

The effect of aging on type I, II, and X collagen in the mandibular condyle was histologically and immunohistochemically assessed in 1−, 4−, 9−, and 16-month-old rats. Hypertrophic chondrocytes, observed in the 4-month-old rat, were absent in the 9-month-old. In 9- and 16-month-old rats, a mineralizing front ran parallel to the surface of the condyle, and the calcified cartilage was thicker than in the younger rats. Type I collagen was observed from the fibrous layer to the upper maturative cell layer in the 1- and 4-month-old rats. In the 9-month-old, the type I collagen-positive area extended to the whole cartilaginous region. In the 16-month-old, type I collagen took on an archlike configuration around the lacunae. Intense type II collagen reactivity in the maturative and hypertrophic cell layers of the 1-month-old rat was only slightly changed in the 4-month-old. In the 9-month-old rat, immunoreaction was detected from the proliferative cell layer; this extended to the whole cartilage in the 16-month-old. Type X collagen was localized in the hypertrophic cell layer in the 1-month-old and had expanded over the maturative cell layer in the 4-month-old rat. It was detected beneath the proliferative cell layer in the 16-month-old. Type X collagen was always observed in the area immediately above the mineralizing front of the cartilage matrix. Thus, our study indicated that mandibular condylar cartilage becomes fibrocartilage-like tissue with advancing age and that type X collagen may play a pivotal role in the progression of the mineralized front.     

Efficacy and safety of novel collagen conduits filled with collagen filaments to treat patients with peripheral nerve injury: A multicenter,controlled, open-label clinical trial

IntroductionThe safety and efficacy of using artificial collagen nerve conduits filled with collagen filaments to treat nerve defects has not been fully studied in humans. We conducted a multicenter, controlled, open-label study to compare the safety and efficacy of artificial nerve conduit grafts with those of autologous nerve grafts.MethodsWe included patients with a sensory nerve defect of ≤30 mm, at the level of the wrist or a more distal location, with the first-line surgical methods selected according to a patient’s preference. We compared sensory recovery using static two-point discrimination and adverse events between the artificial collagen nerve conduit and autologous nerve grafting.ResultsThe artificial nerve conduit group included 49 patients, with a mean age of 42 years and nerve defect of 12.6 mm. The autologous nerve graft group included 7 patients, with historical data of an additional 31 patients, with a mean age of 36 years and nerve defect of 18.7 mm. The rate of recovery of sensory function at 12 months was 75% (36/49) for the artificial nerve conduit group and 73.7% (28/38) in the autologous nerve group. No serious adverse events directly associated with use of the artificial nerve conduit were identified.ConclusionsThe treatment of nerve defects ≤30 mm using artificial collagen nerve conduits was not inferior to treatment using autologous nerve grafts. Based on our data, the new artificial collagen nerve conduit can provide an alternative to autologous nerve for the treatment of peripheral nerve defects.     

Expression patterns of collagen types I and III in the capsule of a rat knee contracture model

Our objective was to determine the changes in expression of collagen types I and III in the capsule of a rat knee contracture model. The unilateral knee joints of adult male rats were rigidly immobilized at 150° of flexion using a rigid plastic plate and screws for 3 days, 1, 2, 4, 8, and 16 weeks (immobilized group). Sham‐operated animals had holes drilled in the femur and tibia with screws inserted without a plate (control group). The expression patterns of collagen types I and III in the anterior and posterior capsule were evaluated by in situ hybridization (ISH), quantitative real‐time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Western blotting (WB). Expressions of collagen types I and III were decreased after immobilization compared to the control group by ISH and qPCR. The expression was not changed after immobilization compared to the control group by IHC and WB. The expression of mRNA and protein levels of collagen types I and III were not increased after immobilization, which indicated that accumulation of the two types of collagen was not the etiology of joint contracture. Another process, such as capsule and synovial adhesions, may be one possible cause of joint contracture. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:315–321, 2010     

Radial nerve repair using an autologous denatured muscle graft: comparison with outcomes of nerve graft repair

Summary Background. The efficiency of denatured muscle grafting in nerve repair has been confirmed in experimental models and animals. The first clinical trials to repair digital nerves and mixed sensory-motor nerves were encouraging regarding sensory recovery but motor recovery was poor, probably because of delayed repair. We present the functional outcome of repair of motor nerves using denatured muscle graft and compare the results with those using standard nerve graft techniques. Methods. This prospective study included 9 radial nerve defects repaired with denatured muscle grafts and 23 radial nerve defects repaired using nerve grafts. Missile induced nerve injury, mid-arm level of lesion, a nerve gap smaller than 6 cm, and a preoperative interval of less than 5 months were characteristics shared by all patients. None of the patients had concomitant vascular injury, severe scarring, or significant soft tissue damage in the region of nerve repair. Motor recovery was estimated with 0–5 points, at least 4.7 years after surgery, according to the BMRC scale. Results. A successful outcome (≥M3) was achieved in 7 out of the 9 patients treated using a muscle graft and in 21 out of the 23 patients treated using nerve grafts (P > 0.05). Excellent recovery and the clinically significant re-establishment of thumb extension (M5 grade) were never achieved in the patients treated using muscle grafts. The average motor score was significantly better in patients treated with nerve grafts than in those who received muscle grafts (3.8 ± 0.9 and 3.2 ± 0.8; P = 0.035). With the patients who received muscle grafts, an inverse correlation existed between motor recovery and the length of the nerve gap (P = 0.017). Conclusions. Denatured muscle grafts can be useful for bridging short radial nerve defects, but the quality of recovery is significantly worse than after nerve graft repair. Even if relatively short nerve defects are bridged with denatured muscle grafts, the outcomes correlate inversely with the length of the gap.     

Seeding nerve sutures with minced nerve-graft (MINE-G): a simple method to improve nerve regeneration in rats

Background: The aim of this study was to assess the effect of seeding the distal nerve suture with nerve fragments in rats.

Methods: On 20 rats, a 15?mm sciatic nerve defect was reconstructed with a nerve autograft. In the Study Group (10 rats), a minced 1?mm nerve segment was seeded around the nerve suture. In the Control Group (10 rats), a nerve graft alone was used. At 4 and 12 weeks, a walking track analysis with open field test (WTA), hystomorphometry (number of myelinated fibers (n), fiber density (FD) and fiber area (FA) and soleus and gastrocnemius muscle weight ratios (MWR) were evaluated. The Student t-test was used for statistical analysis.

Results: At 4 and 12 weeks the Study Group had a significantly higher n and FD (p?=?.043 and .033). The SMWR was significantly higher in the Study Group at 12 weeks (p?=?.0207).

Conclusions: Seeding the distal nerve suture with nerve fragments increases the number of myelinated fibers, the FD and the SMWR. The technique seems promising and deserves further investigation to clarify the mechanisms involved and its functional effects.     

Dorsal root repair by means of an autologous nerve graft: Experimental study in the rat

Summary Rat dorsal root regeneration was studied after 6th and 7th cervical root surgical removal and replacement with an autologous graft of peripheral nerve harvested from the surval nerve from dorsal root ganglion to dorsal horn. Histological studies showed axonal regeneration within the grafts. When the distal end of the graft was placed inside the posterior horn of the spinal cord by use of a myelotomy, axonal sprouts (revealed by the transganglionic staining method of horseradish peroxidase or HSP) reached the neurones of the posterior horn in a limited fashion.     

Muscle autografts in nerve gaps. Pattern of regeneration and myelination in various lengths of graft: an experimental study in guinea pigs

Denatured muscle autograft contains large inner basement membrane tubes, which are anatomically and chemically similar to peripheral nerve basement membrane tubes. These autografts can be used for bridging nerve gaps. In 30 Duncan-Hartley guinea pig sciatic nerves, experimentally induced gaps of 5 mm, 10 mm, and 15 mm were bridged with freeze-thawed gluteus maximus muscle autografts. The results were studied for up to 12 weeks. Functional and histological criteria, morphometry, and electron microscopy were used for the evaluation of regeneration and myelination. Functional recovery was seen by 12 weeks in 5-mm grafts. Morphometric study of 1-μm semithin sections was carried out, and the number of axons in each representative field was studied, as the percentage of myelinated and unmyelinated fibers; the thickness of myelin was also measured. The percentage of myelinated and unmyelinated fibers was estimated by transmission electron microscopy (TEM). Axonal repopulation in the distal segment was seen by the third week in the 5-mm graft, and myelination was more extensive in this group in comparison to the others. On morphometric analysis, the mean fiber diameter in the distal part of the graft was 3.81 μm in the 5-mm graft and 2.9 μm in the 15-mm graft at 12 weeks. The results of this experiment prove that the length of the graft is an important consideration for muscle autografts when they are used for mixed peripheral nerve repair. Received: August 23, 2000 / Accepted: June 5, 2001     

The reduction of extraneural scarring with buccal mucosa graft wrapping around the sciatic nerve: an experimental study in a rat model

Background: The postoperative development of epineural and extraneural scar tissue adversely affects peripheral nerve surgery outcomes. Although several surgical methods, pharmacological agents, and chemical materials have been used to prevent epineural scar formation in both clinical and experimental models, the results are still unsatisfactory. The purpose of this study was to investigate the efficacy of buccal mucosa graft (BMG) wrapping on epineural scarring in an adult rat model.

Methods: Bilateral sciatic nerves were carefully exposed in 24 adult Sprague-Dawley rats, and a circumferential segment of epineurium (0.5?cm) was excised from both nerves. The epineurectomised left nerve segment was wrapped with a BMG (experimental side), while the right nerve segment did not receive any surgical procedure other than the epineurectomy, and served as the control side. To perform gross and histopathological examinations, 12 randomly selected rats were euthanised at 4 weeks postoperatively, and the remaining rats were euthanised at 8 weeks.

Results: The left sciatic nerve that was wrapped with a BMG following epineurectomy showed significantly less nerve adhesion at 8 weeks (p?=?.018), and less epineural scar tissue at both 4 (p?=?.014) and 8 weeks (p?=?.025). Inflammation of the BMG-wrapped nerves was increased at 4 weeks (p?=?.029), but not at 8 weeks.

Conclusion: BMG wrapping decreases postoperative adhesion and scar tissue formation of epineurectomised healthy nerves, despite the presence of increased inflammation in the early postoperative period.     

Reconstruction of a 4-cm human median nerve gap by including an autogenous nerve slice in a bioabsorbable nerve conduit: case report

Nerve gaps up to 3 cm in length can be reconstructed in the human with a bioabsorbable nerve conduit; however, nerve gaps greater than 3 cm have not been reconstructible in animal models unless a neurotrophic factor, like cultured Schwann cells, was added to the nerve conduit. It is the purpose of this article to present the result of human nerve regeneration across a 4-cm nerve gap in the median nerve at the wrist when a slice of autogenous normal nerve was placed into the middle of a bioabsorbable nerve conduit.     

Changes in serum carboxyterminal telopeptide of type I collagen in an experimental model of canine osteomyelitis

Blood biochemical indices of bone turnover were followed up for 1 month in six dogs with experimental osteomyelitis. The bone infection resulted in significant increase in parameters of bone formation (serum bone alkaline phosphatase and serum osteocalcin) and bone resorption [serum carboxyterminal telopeptide of type I collagen (i-ICTP)] as early as the end of the second week after the operation and inoculation. There was strong evidence that serum i-ICTP levels could be useful for the early diagnosis of postoperative complications in veterinary orthopedics, such as posttraumatic osteomyelitis.     

外源性表皮生长因子促进鼠坐骨神经再生的实验研究

目的 评价外源性表皮生长因子（exogenous epidemal growth factor,EGF）对神经再生的影响。方法 雄性SD大鼠48只,建立成鼠坐骨神经挤压伤模型。按术后注射药物的不同成分2组,每组24只鼠。损伤对照组：在神经损伤处注射生理盐水5μl;EGF组：注射EGF／生理盐水液（10μg/5μl）。于术后2、4、6周3个时间点测定坐骨神经功能指数、CMAP的潜伏期、最大语诱发电位的恢复率、组织学检测、电镜超微结构观察。结果 坐骨神经功能指数恢复率在各时间点,EGF组无明显优于对照组（P＜0．01）。CMAP潜伏期的延迟率,EGF组明显小于对照组（P＜0．01）;诱发电位恢复率EGF组明显好于对照组（P＜0．01）。组织学检查：有髓神经纤维数在术后2、4周时EGF组明显多于对照组（P＜0．01）;各时间点有髓神经纤维直径及截面积,EGF组明显优于对照组（P＜0．01）。超微结构观察：EGF组再生神经的有髓纤维数,髓鞘厚度,髓鞘的成熟度明显好于对照组。结论 外源性EGF对神经的再生和功能恢复有一定的作用。     

Low‐intensity pulsed ultrasound (LIPUS) increases the articular cartilage type II collagen in a rat osteoarthritis model

In this study, the effect of low‐intensity pulsed ultrasound (LIPUS) on cartilage was evaluated in a rat osteoarthritis (OA) model using serum biomarkers such as CTX‐II (type II collagen degradation) and CPII (type II collagen synthesis) as well as histological criteria (Mankin score and immunohistochemical type II collagen staining). OA was surgically induced in the knee joint of rats by anterior cruciate/medial collateral ligament transection and medial meniscus resection (ACLT + MMx). Animals were divided into three groups: sham‐operated group (Sham), ACLT + MMx group without LIPUS (?LIPUS), and ACLT + MMx group with LIPUS (+LIPUS; 30 mW/cm², 20 min/day for 28 days). CTX‐II levels were elevated in both ?LIPUS and +LIPUS groups compared to that in the Sham group after the operation, but there was no significant difference between +LIPUS and ?LIPUS groups, suggesting that LIPUS does not affect the degradation of type II collagen in this model. In contrast, CPII was significantly increased in +LIPUS group compared to ?LIPUS and Sham. Moreover, histological damage on the cartilage (Mankin score) was ameliorated by LIPUS, and type II collagen was immunohistochemically increased by LIPUS in the cartilage of an OA model. Of interest, mRNA expression of type II collagen was enhanced by LIPUS in chondrocytes. Together these observations suggest that LIPUS is likely to increase the type II collagen synthesis in articular cartilage, possibly via the activation of chondrocytes and induction of type II collagen mRNA expression, thereby exhibiting chondroprotective action in a rat OA model. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:361–369, 2010     

Low-power laser biostimulation enhances nerve repair after end-to-side neurorrhaphy: a double-blind randomized study in the rat median nerve model

Previous studies have shown that low-power laser biostimulation (lasertherapy) promotes posttraumatic nerve regeneration. The objective of the present study was to investigate the effects of postoperative lasertherapy on nerve regeneration after end-to-side neurorrhaphy, an innovative technique for peripheral nerve repair. After complete transection, the left median nerve was repaired by end-to-side neurorrhaphy on the ulnar donor nerve. The animals were then divided into four groups: one placebo group, and three laser-treated groups that received lasertherapy three times a week for 3 weeks starting from postoperative day 1. Three different types of laser emission were used: continuous (808 nm), pulsed (905 nm), and a combination of the two. Functional testing was carried out every 2 weeks after surgery by means of the grasping test. At the time of withdrawal 16 weeks postoperatively, muscle mass recovery was assessed by weighing the muscles innervated by the median nerve. Finally, the repaired nerves were withdrawn, embedded in resin and analyzed by light and electron microscopy. Results showed that laser biostimulation induces: (1) a statistically significant faster recovery of the lesioned function; (2) a statistically significant faster recovery of muscle mass; (3) a statistically significant faster myelination of the regenerated nerve fibers. From comparison of the three different types of laser emissions, it turned out that the best functional outcome was obtained by means of pulsed-continuous-combined laser biostimulation. Taken together, the results of the present study confirm previous experimental data on the effectiveness of lasertherapy for the promotion of peripheral nerve regeneration and suggest that early postoperative lasertherapy should be considered as a very promising physiotherapeutic tool for rehabilitation after end-to-side neurorrhaphy.     

Effects of collagen nerve guide on neuroma formation and neuropathic pain in a rat model

BACKGROUND: Posttraumatic neuroma formation is a major cause of neuropathic pain that can occur after elective surgery, amputation, or trauma. This study examined the use of biosynthetic collagen nerve guides to prevent the development of posttraumatic neuromas. METHODS: Collagen nerve guides were applied after neurectomy in a rat sciatic nerve model in an effort to stimulate linear neuronal outgrowth and reduce random axon sprouting. Animals were monitored for evidence of neuropathic pain--autotomy scores were recorded for 8 weeks posttransection--after which proximal stumps were excised and processed for histologic analyses. RESULTS: Moderate to severe autotomy was observed in 88% (7 of 8) of the control (neurectomy) animals. In contrast, 13% (1 of 8) of animals receiving collagen nerve guides developed autotomy, which was significantly less than controls (P < .01). Qualitative analyses of neurofilament and Schwann cell-labeled nerve sections showed a significant enhancement in Schwann cell migration away from the proximal stump and advanced linear axonal regrowth in the collagen nerve guide-treated animals. CONCLUSIONS: Collagen nerve guides alter the regrowth of transected nerves and reduce the severity of symptoms associated with neuropathic pain.     

N-terminal telopeptides of type I collagen and bone mineral density for early diagnosis of nonunion: An experimental study in rabbits

Background:The diagnosis and treatment of bone nonunion have been studied extensively. Diagnosis and treatment of nonunion are mainly performed based on the interpretation of clinico-radiographic findings, which depend on the clinician''s experience and the degree of bone callus formation during the fracture-healing process. However, resolution may be compromised when the bone mineral content is <25%. A feasible method of monitoring bone-healing is therefore needed. We monitored a rabbit model of bone nonunion by regular radiographic examinations, QCT detection, and biomarker concentrations.Results:BMD and NTX concentrations were significantly lower at 5 weeks postoperatively compared to the preoperative values and were significantly different between the two groups. OC showed no significant difference before and after surgery.Conclusions:BMD and NTX concentrations may be useful for early detection of bone nonunion in rabbits.     

Sciatic nerve repair with tissue engineered nerve: Olfactory ensheathing cells seeded poly(lactic-co-glygolic acid) conduit in an animal model

Background and Aim:

Synthetic nerve conduits have been sought for repair of nerve defects as the autologous nerve grafts causes donor site morbidity and possess other drawbacks. Many strategies have been investigated to improve nerve regeneration through synthetic nerve guided conduits. Olfactory ensheathing cells (OECs) that share both Schwann cell and astrocytic characteristics have been shown to promote axonal regeneration after transplantation. The present study was driven by the hypothesis that tissue-engineered poly(lactic-co-glycolic acid) (PLGA) seeded with OECs would improve peripheral nerve regeneration in a long sciatic nerve defect.

Materials and Methods:

Sciatic nerve gap of 15 mm was created in six adult female Sprague-Dawley rats and implanted with PLGA seeded with OECs. The nerve regeneration was assessed electrophysiologically at 2, 4 and 6 weeks following implantation. Histopathological examination, scanning electron microscopic (SEM) examination and immunohistochemical analysis were performed at the end of the study.

Results:

Nerve conduction studies revealed a significant improvement of nerve conduction velocities whereby the mean nerve conduction velocity increases from 4.2 ΁ 0.4 m/s at week 2 to 27.3 ΁ 5.7 m/s at week 6 post-implantation (P < 0.0001). Histological analysis revealed presence of spindle-shaped cells. Immunohistochemical analysis further demonstrated the expression of S100 protein in both cell nucleus and the cytoplasm in these cells, hence confirming their Schwann-cell-like property. Under SEM, these cells were found to be actively secreting extracellular matrix.

Conclusion:

Tissue-engineered PLGA conduit seeded with OECs provided a permissive environment to facilitate nerve regeneration in a small animal model.