Immediate mobilization of distal radius fractures stabilized by volar locking plate results in a better short-term outcome than a five week immobilization: A prospective randomized trial.

OBJECTIVE: To evaluate the impact of immediate (first day after surgery) mobilization compared to standard five weeks cast immobilization on the functional outcome after volar locking plate fixation of distal radius fractures. DESIGN: Prospective randomized parallel group comparative trial. SETTING: Trauma Hospital, Austria. PARTICIPANTS: Patients with isolated unstable distal radius fractures, stabilized with volar angular stable locking plate. INTERVENTIONS: The immediate mobilization group received a removable forearm splint for one week and active supervised group physiotherapy and home exercises for the shoulder, elbow, wrist, and fingers from the first postoperative day. The cast immobilization group received a non-removable cast for five weeks. In the first five weeks supervised group physiotherapy and home exercises were performed for shoulder, elbow, and fingers. Thereafter additional supervised and home exercises for the wrist were started. MAIN MEASURES: At regular intervals of six and nine weeks, three and six months, and one year post surgery range of motion, grip strength, and x-rays were evaluated. Additionally, the shortened disabilities of the arm, shoulder and hand (QuickDASH) score, Patient-rated Wrist Evaluation, Mayo Wrist score, and pain according to the Visual Analog Scale score were analyzed. RESULTS: One hundred and sixteen patients were prospectively randomized into two study groups. At the one-year follow-up, patients in the immediate mobilization group showed a significantly higher range of motion in extension/flexion (mean difference 10.2°, 99% confidence interval 0.6-19.8), grip strength (mean difference 5.1 kg, 99% confidence interval -0.5 to 10.7), and Mayo Wrist score (mean difference 7.9 points, 99% confidence interval 2.3-13.5) than the cast immobilization group. Range of motion in supination/pronation (mean difference 13.4°, 99% confidence interval 1.5-25.3) and in radial/ulnar deviation (mean difference 6.3°, 99% confidence interval 0.9-11.7) differed significantly up to nine weeks favoring the immediate mobilization group. The Patient-rated Wrist Evaluation revealed significantly better scores after three months (mean difference 9.3 points, 99% confidence interval 0.5-18.1) and QuickDASH after six months (mean difference 7.3 points, 99% confidence interval 0.3-14.3) in the immediate mobilization group. All other subsequent follow-up examinations indicated no significant differences in respect of pain, range of motion, and patient-reported outcome measurements between the study groups. There were no significant differences in respect of radiological loss of reduction and complications between the groups. CONCLUSIONS: Immediate mobilization in combination with supervised physiotherapy of the wrist after volar locking plate fixation of unstable distal radius fractures results in a significantly improved range of motion and grip strength after one year compared to cast immobilization. No increased risk for loss of reduction and other complications was observed.

Antibody seroprevalence and rate of asymptomatic infections with SARS-CoV-2 in Austrian hospital personnel.

BACKGROUND: The aims of this study are to determine (i) SARS-CoV-2 antibody positive employees in Austrian trauma hospitals and rehabilitation facilities, (ii) number of active virus carriers (symptomatic and asymptomatic) during the study, (iii) antibody decline in seropositive subjects over a period of around 6 months, (iv) the usefulness of rapid antibody tests for outpatient screening. METHOD: A total of 3301 employees in 11 Austrian trauma hospitals and rehabilitation facilities of the Austrian Social Insurance for Occupational Risks (AUVA) participated in this open uncontrolled prospective cohort study. Rapid lateral flow tests, detecting a combination of IgM and IgM against SARS-CoV-2), two different types of CLIA (Diasorin, Roche), RT-PCR tests and serum neutralization tests (SNTs) were performed. The tests were conducted twice, with an interval of 42.4 ± 7.7 (Min = 30, Max = 64) days. Positive participants were re-tested with CLIA/SNT at a third time point after 188.0 ± 12.8 days. RESULTS: Only 27 out of 3301 participants (0.82%) had a positive antibody test at any time point during the study confirmed via neutralization test. Among positively tested participants in either test, 50.4% did not report any symptoms consistent with common manifestations of COVID-19 during the study period or within the preceding 6 weeks. In the group who tested positive during or prior to study inclusion the most common symptoms of an acute viral illness were rhinitis (21.9%), and loss of taste and olfactory sense (21.9%). Based on the neutralization test as the true condition, the rapid antibody test performed better on serum than whole blood as 84.6% instead of 65.4% could be detected correctly. Concerning both CLIA tests overall the Roche test detected 24 (sensitivity = 88.9%) and the Diasorin test 22 positive participants (sensitivity = 81.5%). In participants with a positive SNT result, a significant drop in neutralizing antibody titre from 31.8 ± 22.9 (Md = 32.0) at T1 to 26.1 ± 17.6 (Md = 21.3) at T2 to 21.4 ± 13.4 (Md = 16.0) at T3 (χ2 = 23.848, df = 2, p < 0.001) was observed (χ2 = 23.848, df = 2, p < 0.001)-with an average time of 42.4 ± 7.7 days between T1 and T2 and 146.9 ± 13.8 days between T2 and T3. CONCLUSIONS: During the study period (May 11th-August 3rd) only 0.82% were tested positive for antibodies in our study cohort. The antibody concentration decreases significantly over time with 14.8% (4 out of 27) losing detectable antibodies.

Successful salvage via re-osseointegration of a loosened implant in a patient with transtibial amputation.

CASE DESCRIPTION: Osseointegration is a relatively new technique for prosthetic limb attachment that offers various improvements for patients with amputation and facilitates joint preservation. We present a case of implant loosening during rehabilitation in a patient with transtibial amputation that was successfully managed through a combination of measures, aiming to promote re-osseointegration of the implant. OBJECTIVES: Not much is known about structured management of adverse events after osseointegration. Septic or aseptic loosening is currently regarded as implant failure, prompting removal and possible re-implantation at a later stage. The objective of this case report was to evaluate the feasibility of salvaging a loosened implant. STUDY DESIGN: Case report. TREATMENT: A novel treatment approach was employed to enable renewed osseointegration of the implant. First, the bone-implant interface was disrupted and renewed through axial rotation and distal repositioning of the implant. Afterwards, extracorporal shockwave therapy and antibiotic treatment were administered. Prosthetic rehabilitation was then started anew. Regular follow-up x-rays and clinical evaluations were conducted, including standardized outcome tests. OUTCOMES: These combined measures led to a successful re-osseointegration of the implant. In a 21-month follow-up, the patient regained a stable and secure gait pattern, using his prosthesis every day for 15 hours and scoring above average on standardized outcome measures. CONCLUSION: This represents the first report of implant salvage after failed primary osseointegration. As the associated risks of this novel treatment are very low, investigations are warranted to evaluate this approach on a larger scale.

Use of the CatWalk gait analysis system to assess functional recovery in rodent models of peripheral nerve injury - a systematic review.

Injuries of the peripheral nervous system are common among the population affecting around 3% of all trauma patients. This high clinical need in the field of peripheral nerve injury and regeneration has been steadily driving experimental and epidemiological research. Thereby, it is crucial to determine the exact degree of recovery of end-organ function. Regeneration after nerve injuries is assessed by a wide variety of techniques and pre-clinical model systems, where rodent models are among the most widely used. However, results from rodents are difficult to translate to human patients in general, and reproducible and comparable assessment of functional recovery is of highest importance. Computerized gait analysis allows comprehensive acquisition of locomotor function. As the animals cross the recording device voluntarily, functional recovery is assessable with a minimum degree of human interference on their behavior. This article aims to give a detailed overview on the existing literature on CatWalk gait analysis in rodent models of peripheral nerve injuries of upper and lower extremities, e.g. axonotmesis, neurotmesis or fibrosis, with special emphasis on differences between models. Researchers interested in assessment of locomotor function in such models will especially benefit from this work as it will provide them with an overview of the various experimental setups and expected outcomes. This work also addresses potential pitfalls and hurdles in order to promote well designed, comparable studies allowing for accelerated development of therapeutic strategies in peripheral repair and regeneration.

[Palmar radioscapholunate arthrodesis with distal scaphoidectomy]. / Radioskapholunäre Arthrodese mit Entfernung des distalen Skaphoidpols von palmar.

OBJECTIVE: Radioscapholunate (RSL) arthrodesis with distal scaphoidectomy using an angular stable plate and palmar access in post-traumatic or degenerative osteoarthritis limited to the radiocarpal joint. INDICATIONS: Osteoarthritis limited to the radiocarpal joint with intact mediocarpal joint after malunited intra-articular distal radius fractures, rheumatoid osteoarthritis, scapholunate advanced collapse (SLAC) up to stage II. CONTRAINDICATIONS: Mediocarpal osteoarthritis, poor patient compliance, SLAC from stage III, osteitis. SURGICAL TECHNIQUE: The palmar RSL arthrodesis is performed using the palmar approach between the flexor carpi radialis tendon and the radial artery. After releasing the pronator quadratus muscle, a longitudinal capsulotomy is performed and the radiocarpal joint is inspected. After correction of a volar or dorsal intercalated segmental instability of the lunate, the lunate is temporarily fixed to the scaphoid using a K-wire. The distal quarter of the scaphoid and the palmar rim of the distal radius is resected and the cartilage between the scaphoid, lunate and distal radius is removed. The scaphoid and lunate are temporarily fixed to the distal radius using K­wires. Under image intensifier control the angular stable low-profile plate (e.g., volar 2.5 Trilock RSL Fusion plate [Medartis® Aptus® Basel, Switzerland]) is fixed to the distal radius in the long-leg hole. The scaphoid and lunate are fixed distally with two screws each. The carpus is pushed distally using a Codeman distractor and the cancellous bone graft is impacted. Finally, the shaft is fixed with angular stable screws. POSTOPERATIVE MANAGEMENT: Immobilization using a plaster cast or thermoplastic short-arm orthosis for 5 weeks. After 2 weeks, the orthosis can be removed during hand therapy with active wrist and finger exercises. Normal activities permitted after 12 weeks. RESULTS: Palmar RSL arthrodesis and distal scaphoidectomy using angular stable plate fixation shows a high union rate and pain relief while maintaining good residual mobility of the wrist.

Convincing long-term results independent from the postoperative leg alignment following cementless total knee arthroplasty.

BACKGROUND: Cementless primary total knee arthroplasty shows numerous advantages compared with cemented implants (e.g., shorter operation time, preservation of the bone stock). Up to now an increasing number of clinical long-term studies exist. Despite this fact, there is no evidence about the influence of the postoperative leg alignment on the results of cementless knee arthroplasty. There is no work on the clinical outcome of the specific implant, which was used in this study (VANGUARD®, ZimmerBiomet). The purpose of this study was to assess the clinical and radiological long-term results after cementless knee arthroplasty in relation to the postoperative mechanical leg alignment. METHODS: Clinical and radiological results were retrospectively assessed in 83 patients at 10.3 years (ranging from 9.6 to 11.8 years) after implantation. Hip-knee-ankle angle (HKA) was measured, and the patients were separated into a corrected (HKA between three degrees of varus and three degrees of valgus, n = 60) and a varus/valgus (HKA > 3° of varus and valgus, n = 23) group. RESULTS: Up to the time of the clinical follow-up, three out of 83 patients already underwent a revision surgery due to a deep infection (3.6%). Tegner-Lysholm Knee scale was 89.1 in the corrected group and 88.8 in the varus/valgus group (p = .94). The mean Knee Injury and Osteoarthritis Outcome score (KOOS) was 81.2 in the corrected group and 82.4 in the varus/valgus group (p = .63). CONCLUSIONS: Results of this study showed convincing clinical and radiological results after primary cementless knee arthroplasty. Under- or overcorrected postoperative mechanical leg alignments did not influence the long-term clinical results.

Spatiotemporal Differences in Gene Expression Between Motor and Sensory Autografts and Their Effect on Femoral Nerve Regeneration in the Rat.

To improve the outcome after autologous nerve grafting in the clinic, it is important to understand the limiting variables such as distinct phenotypes of motor and sensory Schwann cells. This study investigated the properties of phenotypically different autografts in a 6 mm femoral nerve defect model in the rat, where the respective femoral branches distally of the inguinal bifurcation served as homotopic, or heterotopic autografts. Axonal regeneration and target reinnervation was analyzed by gait analysis, electrophysiology, and wet muscle mass analysis. We evaluated regeneration-associated gene expression between 5 days and 10 weeks after repair, in the autografts as well as the proximal, and distal segments of the femoral nerve using qRT-PCR. Furthermore we investigated expression patterns of phenotypically pure ventral and dorsal roots. We identified highly significant differences in gene expression of a variety of regeneration-associated genes along the central - peripheral axis in healthy femoral nerves. Phenotypically mismatched grafting resulted in altered spatiotemporal expression of neurotrophic factor BDNF, GDNF receptor GFRα1, cell adhesion molecules Cadm3, Cadm4, L1CAM, and proliferation associated Ki67. Although significantly higher quadriceps muscle mass following homotopic nerve grafting was measured, we did not observe differences in gait analysis, and electrophysiological parameters between treatment paradigms. Our study provides evidence for phenotypic commitment of autologous nerve grafts after injury and gives a conclusive overview of temporal expression of several important regeneration-associated genes after repair with sensory or motor graft.

Open reduction and fixation with a locking plate without bone grafting is a reasonable and safe option for treating proximal humerus nonunion.

AIM OF THE STUDY: The aim of this study was to evaluate union rate and clinical outcome in patients with proximal humeral nonunions treated by open reduction and locking plate fixation without bone grafting. METHODS: From 2011 to 2016, nine patients were treated using open reduction and locking plate stabilization without bone grafting. They were examined both clinically and radiologically, with a mean follow-up period of 31 months. Outcome was evaluated using pain and range of motion (ROM) parameters. In addition, self-assessment by patients was registered on the Disability of the Arm, Shoulder and Hand score, Constant-Murley Score, Oxford Shoulder Score, and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form. A CT scan of the shoulder was performed to analyze union. RESULTS: At checkup, all patients showed union in the CT scans, where the mean ROM in abduction was 139° (SD 50°), in adduction 39° (SD 8°), in forward flexion 136° (SD 40°), in extension 44° (SD 11°), in internal rotation 62° (SD 15°), and external rotation 54° (SD 31°). ROM improved significantly in all planes of motion, except for adduction, post-surgery (p < 0.05). Plate removal was necessary in three patients. No complications were reported. CONCLUSION: Open reduction and locking plate fixation without bone grafting is a reasonable and safe option for treating proximal humerus nonunion. It leads to a high union rate, significant improvement in ROM, and in the majority of the cases to an "excellent" and "good" functional outcome without an increased risk of complications.

Volar Radioscapholunate Arthrodesis and Distal Scaphoidectomy After Malunited Distal Radius Fractures.

PURPOSE: The purpose of this study was to assess range of motion (ROM), pain, and incidence of radiographic degenerative joint disease (DJD) after volar radioscapholunate (RSL) arthrodesis and distal scaphoidectomy (DSE) following malunited distal radius fractures (DRF). METHODS: Fourteen patients with malunited DRF and DJD limited to the radiocarpal joint underwent RSL arthrodesis and DSE between 2006 and 2014. These were retrospectively analyzed both clinically and radiologically. Eleven patients with a mean follow-up of 63 months (range, 30-97 months) were included in the final analysis because 1 was unavailable and 2 had died. The outcome was evaluated using parameters of pain, ROM, grip strength, nonunion rate, and DJD of the adjacent joints. In addition, self-assessment by patients was registered on the Disability of the Arm, Shoulder and Hand score, Patient-Rated Wrist Evaluation score, and Michigan Hand Outcomes Questionnaire. To investigate DJD and union, a computed tomography (CT) scan at the final follow-up visit was performed. RESULTS: All patients showed union and no midcarpal DJD in the CT scans at final follow-up. The mean ROM in extension was 53°, flexion 42°, supination 81°, pronation 85°, radial deviation 10° and ulnar deviation 25°. The ROM in extension, extension/flexion arc, and supination improved significantly after surgery. Patients achieved a mean of 80% of grip strength compared with the other hand. CONCLUSIONS: Volar angular stable plate RSL arthrodesis with resection of the distal scaphoid pole is a safe and effective method for treating malunited DRF. This leads to an improved ROM and low pain level. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

A novel experimental rat model of peripheral nerve scarring that reliably mimics post-surgical complications and recurring adhesions.

Inflammation, fibrosis and perineural adhesions with the surrounding tissue are common pathological processes following nerve injury and surgical interventions on peripheral nerves in human patients. These features can reoccur following external neurolysis, currently the most common surgical treatment for peripheral nerve scarring, thus leading to renewed nerve function impairment and chronic pain. To enable a successful evaluation of new therapeutic approaches, it is crucial to use a reproducible animal model that mimics the main clinical symptoms occurring in human patients. However, a clinically relevant model combining both histological and functional alterations has not been published to date. We therefore developed a reliable rat model that exhibits the essential pathological processes of peripheral nerve scarring. In our study, we present a novel method for the induction of nerve scarring by applying glutaraldehyde-containing glue that is known to cause nerve injury in humans. After a 3-week contact period with the sciatic nerve in female Sprague Dawley rats, we could demonstrate severe intra- and perineural scarring that resulted in grade 3 adhesions and major impairments in the electrophysiological peak amplitude compared with sham control (P=0.0478). Immunohistochemical analysis of the nerve structure revealed vigorous nerve inflammation and recruitment of T cells and macrophages. Also, distinct nerve degeneration was determined by immunostaining. These pathological alterations were further reflected in significant functional deficiencies, as determined by the analysis of relevant gait parameters as well as the quantification of the sciatic functional index starting at week 1 post-operation (P<0.01). Moreover, with this model we could, for the first time, demonstrate not only the primary formation, but also the recurrence, of severe adhesions 1 week after glue removal, imitating a major clinical challenge. As a comparison, we tested a published model for generating perineural fibrotic adhesions, which did not result in significant pathological changes. Taken together, we established an easily reproducible and reliable rat model for peripheral nerve scarring that allows for the effective testing of new therapeutic strategies.

Early Rehabilitation of Distal Radius Fractures Stabilized by Volar Locking Plate: A Prospective Randomized Pilot Study.

Background Distal radius fractures are very common and an increased incidence of 50% is estimated by 2030. Therefore, both operative and postsurgical treatment remains pertinent. Main aim in treating intra-articular fractures is to restore the articular surface by internal fixation and early mobilization (EM). Questions/Purposes The purpose of this study was to compare functional results between EM immediately after surgery and 5 weeks of immobilization (IM). Patients and Methods In a randomized prospective study, 30 patients with an isolated distal radius fracture were treated by open reduction and internal fixation using a single volar locking plate excluding bone graft. Fifteen patients were randomized in the EM group and 15 in the IM group. At 6 weeks, 9 weeks, 3 months, 6 months, and 1 year postsurgery, range of motion, grip strength and X-rays were evaluated. Additionally, Quick Disability of the Arm, Shoulder and Hand (QuickDASH) questionnaire, Patient-Rated Wrist Evaluation (PRWE), modified Green O'Brien (Mayo) score, and pain according to the Visual Analog Scale score were analyzed. Results Patients in the EM group had a significantly better range of motion in the sagittal plane, in grip strength up to 6 months, in the frontal plane up to 9 weeks, and in forearm rotation up to 6 weeks. Also QuickDASH and PRWE scores were better up to 6 weeks postsurgery. The Green O'Brien score differed significantly up to 1 year. At 1 year, 93% "excellent" and "good" results in the Green O'Brien score with a mean QuickDASH of 5.98 ± 10.94 and PRWE score of 4.27 ± 9.23 were observed in the EM group. No differences regarding loss of reduction, pain, duration of physiotherapy, and sick leave were noted. Conclusion EM of surgically treated distal radius fractures (without bone graft) is a safe method for postoperative aftercare and leads to an improved range of motion and grip strength at 6 months postsurgery compared with an IM of 5 weeks. Level of Evidence This is a level Ib clinical study.

A therapeutic shock propels Schwann cells to proliferate in peripheral nerve injury.

Damage to the peripheral nervous system (PNS) is a prevalent issue and represents a great burden to patients. Although the PNS has a good capacity for regeneration, regeneration over long distances poses several difficulties. Several recent studies have addressed Schwann cells' limited proliferative capacity; however, a solution has yet to be found. Here, we examine the effects of extracorporeal shock wave therapy (ESWT) on Schwann cell isolation, culture, and proliferation rate. The study conducted demonstrated that Schwann cells treated with ESWT had significantly improved isolation, culture, and proliferative capacities. These findings represent a solution to a significant problem that hospitals and health-care providers face every year: how to treat long distance damage to the PNS with the limited proliferative capabilities of Schwann cells. Although these findings are promising, further studies must be conducted to address the molecular mechanisms by which ESWT alters Schwann cells and the potential implications for peripheral nerve damage and other prevalent illnesses. This study is a review article. Referred literature in this paper has been listed in the references part. The datasets supporting the conclusions of this article are available online by searching the PubMed. Some original points in this article come from the laboratory practice in our research centers and the authors' experiences.

A New Preparation Method for Anisotropic Silk Fibroin Nerve Guidance Conduits and Its Evaluation In Vitro and in a Rat Sciatic Nerve Defect Model.

Over the past decade, silk fibroin (SF) has been emergently used in peripheral nerve tissue engineering. Current approaches aiming at producing SF-based nerve guidance conduits (SF-NGCs) used dissolved silk based on either aqueous solutions or organic solvents. In this study, we describe a novel procedure to produce SF-NGCs: A braided tubular structure of raw Bombyx mori silk is subsequently processed with the ternary solvent CaCl2/H2O/ethanol, formic acid, and methanol to improve its mechanical and topographical characteristics. Topographically, the combination of the treatments results in a fusion of the outer single silk fibers to a closed layer with a thickness ranging from about 40 to 75 µm. In contrast to the outer wall, the inner lumen (not treated with processing solvents) still represents the braided structure of single fibers. Mechanical stability, elasticity, and kink characteristics were evaluated with a custom-made test system. The modification procedure described here drastically improved the elastic properties of our tubular raw scaffold, favoring its use as a NGC. A cell migration assay with NIH/3T3-fibroblasts revealed the impermeability of the SF-NGC wall for possible invading and scar-forming cells. Moreover, the potential of the SF-NGC to serve as a substratum for Schwann cells has been demonstrated by cytotoxicity tests and live-dead stainings of Schwann cells grown on the inner surface of the SF-NGC. In vivo, the SF-NGC was tested in a rat sciatic nerve injury model. In short-term in vivo studies, it was proved that SF-NGCs are not triggering host inflammatory reactions. After 12 weeks, we could demonstrate morphological and functional reinnervation of the distal targets. Filled with collagen, a higher number of axons could be found in the distal to the graft (1678±303), compared with the empty SF-NGC (1274±146). The novel SF-NGC presented here shows promising results for the treatment of peripheral nerve injuries. The modification of braided structures to adapt their mechanical and topographical characteristics may support the translation of SF-based scaffolds into the clinical setting. However, further improvements and the use of extracellular matrix molecules and Schwann cells are suggested to enable silk tube based conduits to bridge long-distance nerve gaps.

Low level light therapy by LED of different wavelength induces angiogenesis and improves ischemic wound healing.

BACKGROUND AND OBJECTIVE: Low-level light therapy (LLLT) has been revealed as a potential means to improve wound healing. So far, most studies are being performed with irradiation in the red to near-infrared spectra. Recently, we showed that blue light (470 nm) can significantly influence biological systems such as nitric oxide (NO) metabolism and is able to release NO from nitrosyl-hemoglobin or mitochondrial protein complexes. Therefore, the aim of this study was to evaluate and compare the therapeutic value of blue or red light emitting diodes (LEDs) on wound healing in an ischemia disturbed rodent flap model. STUDY DESIGN/MATERIALS AND METHODS: An abdominal flap was rendered ischemic by ligation of one epigastric bundle and subjected to LED illumination with a wavelength of 470 nm (blue, n = 8) or 629 nm (red, n = 8) each at 50 mW/cm(2) and compared to a non-treated control group (n = 8). Illumination was performed for 10 minutes on five consecutive days. RESULTS: LED therapy with both wavelengths significantly increased angiogenesis in the sub-epidermal layer and intramuscularly (panniculus carnosus muscle) which was associated with significantly improved tissue perfusion 7 days after the ischemic insult. Accordingly, tissue necrosis was significantly reduced and shrinkage significantly less pronounced in the LED-treated groups of both wavelengths. CONCLUSIONS: LED treatment of ischemia challenged tissue improved early wound healing by enhancing angiogenesis irrespective of the wavelength thus delineating this noninvasive means as a potential, cost effective tool in complicated wounds.

Inhibition of calpains fails to improve regeneration through a peripheral nerve conduit.

Intramuscular injection of the calpain inhibitor leupeptin promotes peripheral nerve regeneration in primates (Badalamente et al., 1989 [13]), and direct positive effects of leupeptin on axon outgrowth were observed in vitro (Hausott et al., 2012 [12]). In this study, we applied leupeptin (2mg/ml) directly to collagen-filled nerve conduits in the rat sciatic nerve transection model. Analysis of myelinated axons and retrogradely labeled motoneurons as well as functional 'CatWalk' video analysis did not reveal significant differences between vehicle controls and leupeptin treated animals. Therefore, leupeptin does not improve nerve regeneration via protease inhibition in regrowing axons or in surrounding Schwann cells following a single application to a peripheral nerve conduit suggesting indirect effects on motor endplate integrity if applied systemically.

The use of shock waves in peripheral nerve regeneration: new perspectives?

Low-energy extracorporeal shock wave treatment (ESWT) is a relatively new therapeutic tool that is widely used for the treatment of epicondylitis and plantar fasciitis and to foster bone and wound healing. Shock waves, sonic pulses with high energy impact, are thought to induce biochemical changes within the targeted tissues through mechanotransduction. The biological effects of ESWT are manifested in improved vascularization, the local release of growth factors, and local anti-inflammatory effects, but the target cells too are influenced. ESWT appears to have differential effects on peripheral nerves and has been proved to promote axonal regeneration after axotomy. This review discusses the effects of ESWT on intact and injured peripheral nerves and suggests a multiple mechanism of action.

The optimal carrier for BMP-2: a comparison of collagen versus fibrin matrix.

INTRODUCTION: The aim of our study was to investigate in vitro and in a new in vivo rat model for impaired bone healing whether a low dose BMP-2 preparation in fibrin would be equivalent or better than the combination of collagen and a high dose of BMP-2 which is currently in clinical use. MATERIALS AND METHODS: In a 14 day period we compared the in vitro release kinetics of an absorbable collagen sponge (ACS) with 72 µg rhBMP-2 in the BMPC group and fibrin matrix with 10 µg rhBMP-2 in the BMPF group. In our in vivo experiment a critical sized osteotomy was performed in the rat femur, which was filled with a spacer, inhibiting bone formation for a period of 4 weeks. In a second operation this spacer was removed and the test item was applied into the defect. We compared the BMPF and BMPC groups with the ACS alone, FIBRIN alone and the EMPTY (4w/8w) control groups. 4 and 8 weeks after the second operation, specimens were analysed by X-ray and µCT imaging. Mechanically stable femurs were biomechanically evaluated. RESULTS: Cumulative BMP-2 release was five times higher in the BMPF group than in the BMPC group during the observation period. µCT analysis revealed that both the extent of bone union and the bone volume were significantly higher in the group with a lower dose of BMP-2 in fibrin matrix than in the groups without BMP-2 treatment. However there was no statistically significant difference between the BMPF and BMPC groups. CONCLUSION: We conclude that fibrin matrix is an excellent carrier for BMP-2 and that it provides equivalent results with a sevenfold lower dose of BMP-2 compared with ACS.

Improved rate of peripheral nerve regeneration induced by extracorporeal shock wave treatment in the rat.

De-focused low energy extracorporeal shock wave therapy (ESWT) has been widely used in various clinical and experimental models for the treatment of painful conditions such as epicondylitis and plantar fascitis and also bone and wound healing. There is evidence that ESWT improves the metabolic activity of various cell types, e.g. chondrocytes and endothelial cells but little is known about its effects on nervous tissue. The aim of this study was to investigate whether ESWT improves the regeneration of injured nerves in an experimental rat model. Sprague-Dawley rats received an 8mm long homotopic nerve autograft into the right sciatic nerve, fixed with epineurial sutures. Two experimental groups were set up: the group 1 animals received ESWT (300 impulses, 3 Hz) immediately after nerve grafting whereas the group 2 (control) animals received only nerve autografts. Serial CatWalk automated gait analysis, electrophysiological studies and morphological investigations were carried out. The survival time was either 3 weeks or 3 months. At 6 to 8 weeks of survival the ESWT group of animals exhibited a significantly improved functional recovery relative to the controls. Electrophysiological observations at 3 weeks after surgery revealed marked values of amplitude (3.9±0.8 mV, S.E.M.) and compound nerve action potential (CNAP, 5.9±1.4 mV·ms, S.E.M.) in the ESWT group, whereas there were no detectable amplitudes in the control group. This finding was accompanied by significantly greater numbers of myelinated nerve fibres in the middle of the graft (4644±170 [S.E.M., ESWT] vs 877±68 [S.E.M., control]) and in the distal stump (1586±157 [S.E.M., ESWT] vs 308±29 [S.E.M., control]) of ESWT animals relative to the controls 3 weeks after surgery. Three weeks after surgery the nerve grafts of control animals contained great numbers of phagocytes and unmyelinated nerve fibres, while the ESWT nerve grafts were filled with well-myelinated regenerating axons. There was no significant difference between the numbers of endoneural vessels in the ESWT and the control nerves. Three months after surgery, no significant differences were observed in the functional and electrophysiological data. Equally high numbers of myelinated axons distal to the graft could be found in both groups (7693±673 [S.E.M., ESWT] vs 6090±716 [S.E.M., control]). These results suggest that ESWT induces an improved rate of axonal regeneration, this phenomenon probably involving faster Wallerian degeneration, the improved removal of degenerated axons and a greater capacity of the injured axons to regenerate.

An fMRI marker for peripheral nerve regeneration.

Final outcome after surgical repair of peripheral nerve transections varies. Here, we present the first longitudinal functional magnetic resonance imaging (fMRI) observation of cortical somatosensory reorganization patterns after surgery. A 43-year-old man presented with isolated complete transection of the right median nerve and underwent immediate epineural end-to-end coaptation. Applying standardized vibrotactile median nerve stimulation, 3 T brain activation maps were evaluated at 1, 7, 15 weeks and 1 year after surgery. Initially, the affected hemisphere showed no primary activation but increased frontoparietal activity. After 1 year, primary activation had recovered, and frontoparietal activity was decreased relative to the nonaffected hemisphere. Based on these longitudinal fMRI patterns, we propose a new marker for restoration of somatosensory function, which may not be provided by electrophysiological methods.