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Biomedical subjects

G Lundborg

Publications and source records attributed to G Lundborg.

At least 55 records · Page 3Linked to original sources

Bioartificial nerve graft for bridging extended nerve defects in rat sciatic nerve based on resorbable guiding filaments.

A long defect (15 mm) in rat sciatic nerve was repaired with a bioartificial nerve graft composed of a silicone tube and seven synthetic filaments of five types (polyamide, catgut, polydioxanone, and two types of polyglactin, normal and quickly-absorbed) inserted longitudinally into the tube. In all cases in which filaments were used a regenerating bridge was obtained in the tube after three months in contrast to empty silicone tubes, in which no structure was observed. There was a 6%-46% recovery of isometric muscle contractility of the anterior tibial and gastrocnemius muscles with positive pinch reflex test in most cases. Myelinated axons were seen in the regenerating tissue between the filaments but not directly in contact with them, and there were varying numbers of macrophages close to the filaments. Silicone tubes with filaments, regardless of type of filament, induced nerve tissue to regenerate and resulted in functional recovery through a 15 mm nerve gap not achieved with empty tubes. Nerve promoting factors may be applied to the filaments and the model is a valuable tool for further development of artificial nerve grafts.

Animals↗

Sutures alone are sufficient to support regeneration across a gap in the continuity of the sciatic nerve in rats.

We have proposed that it is sufficient to provide a simple substratum on which regenerating axons may traverse a gap in a peripheral nerve. To test this hypothesis we set up a new experimental model in which sutures were used to bridge a 10 mm long defect in a peripheral nerve. A defect was created bilaterally in 25 rat sciatic nerves. The cut ends of the nerve were joined by three laps of a continuous suture, on one side with 8/0 polyamide (non-absorbable) and on the other with 8/0 polyglactin (absorbable), leaving a 7 mm gap. At two weeks a matrix that contained capillaries, fibroblast-like cells, and mononuclear cells had formed between the nerve endings, and the sutures were surrounded by foreign-body-like tissue reactions. At four weeks axons had grown into the distal nerve segment on both sides in 65%-90% of the cases as indicated by a response to the pinch reflex test and immunocytochemistry for presence of neurofilament protein. Axons were organised in minifascicles and these tended to grow larger as the demarcation of the entire regenerated segment by a perineurial-like structure improved with time. At 12 weeks axonal counts of cross-sections of the distal tibial trunk showed many myelinated nerve fibres but no significant difference in axonal counts or degree of myelination between the polyamide and polyglactin sides. The results show that conventional sutures alone are sufficient to support regeneration across a short gap in a peripheral nerve, a method that may be of potential clinical value.

Animals↗

Assessment of functional outcome after nerve repair in a longitudinal cohort.

To investigate the temporal changes in the results of clinical tests of the functional outcome after nerve repair, we followed up 19 patients periodically over a four year period after repair of the median or ulnar nerve at the forearm. Between the first and last follow-up four of the instruments used--Semmes-Weinstein monofilaments, manual muscle testing, Sollerman grip test, and Jamar dynamometer--indicated significant and moderate to large improvements. A moderate and significant improvement was also noted during the same period in patients' estimation of pain or discomfort. Results of the two-point discrimination test did not change significantly over time. Most changes occurred during the first postoperative year, and thereafter it was principally motor function that improved. We conclude that four of the six used tests showed useful temporal dynamics during the follow-up time. The lack of responsiveness in two-point discrimination test suggests that other or complementary test instruments should be used for assessment of tactile gnosis after nerve repair.

Adolescent↗

Osseointegrated proximal interphalangeal joint prostheses with a replaceable flexible joint spacer--long-term results.

Osseointegrated proximal interphalangeal joint prostheses with a replaceable joint spacer were used in 25 joints in 19 patients (five men and 14 women) aged 45 (16-67) years. Indications for surgery were post-traumatic arthrosis (nine joints in eight patients), primary osteoarthrosis (10 joints in eight patients), and rheumatoid arthritis (six joints in three patients). A silicone joint spacer was attached to titanium fixtures by short titanium stems that extended from the spacer and fitted into a central canal in the screws. The arthroplasty was done in one stage, which included resection of the joint followed by grafting of marrow and cancellous bone from the iliac crest into adjacent medullary cavities before insertion of the titanium fixture. Follow up at 8.5 (5-11) years showed that 47 out of 50 fixtures (94%) had successfully osseointegrated while 17 of 25 joint spacers (68%) had fractured. However, because of the design of the prostheses fractured joint spacers could easily be replaced and a new spacer could be connected to already osseointegrated screws. The joint spacer was replaced in 11 fingers once or several times. Range of movement (ROM) in the whole series (four fusions excluded) was 41 (0-85) degrees with an extension defect of 15 (0-55) degrees. In eight joints with permanently intact joint spacers the ROM was 39 (0-60) degrees with extension defects of 16 (0-40) degrees. In six joints in which the spacer was replaced once the ROM was 43 (0-85) degrees with an extension defect of 16 (0-55) degrees. Our data confirm good long-term osseointegration of titanium fixtures and that a joint spacer, if needed, can be replaced by a new spacer that can be attached to already osseointegrated screws without jeopardizing the ROM.

Adolescent↗

Vascular endothelial growth factor stimulates Schwann cell invasion and neovascularization of acellular nerve grafts.

The aim of this study was to investigate the effects of vascular endothelial growth factor (VEGF) on regeneration of the rat sciatic nerve in vivo. To that end we used 10-mm long cell-free nerve grafts to bridge a gap in the sciatic nerve. The grafts were pretreated with either VEGF (50, 100 or 250 ng/ml), nerve growth factor (NGF, 100 ng/ml) or laminin (100 ng/ml) before implantation. Outgrowth of axons, Schwann cells, blood vessels and macrophages were studied 10 days post-implantation by the use of immunocytochemistry and histochemistry. Grafts pretreated with VEGF stimulated the outgrowth of Schwann cells and blood vessels but not axons. In such grafts, the Schwann cells also exhibited a dramatic change in morphology and became filled with large lipid-containing vacuoles. These cells also showed an intense immunoreactivity for the VEGF receptor flk-1. Neither pretreatment with laminin nor NGF affected the outgrowth of Schwann cells. However, NGF treatment increased the number of axons in the graft but was not able to counteract injury-induced downregulation of substance P in the dorsal root ganglia. The results show that local application of VEGF promotes at least two events, invasion of Schwann cells and neovascularization, which are important during nerve regeneration. The findings suggest that the effects of the pretreatment by the growth factors is local and limited to the graft, whereas central events like neuropeptide synthesis is not affected.

Alkaline Phosphatase↗

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open up new perspectives in the coming millennium.

Amputation, Surgical↗

Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system.

Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells, and it promotes angiogenesis in vivo. Here we report that VEGF(165) has neurotrophic actions on cultured adult mouse superior cervical ganglia (SCG) and dorsal root ganglia (DRG), measured as axonal outgrowth. Maximal effect was observed at 10-50 ng/ml for SCG and 100 ng/ml for DRG. VEGF-induced axonal outgrowth was inhibited by the mitogen-activated protein kinase kinase inhibitor PD 98059 but not by the protein kinase inhibitor K252a. VEGF also increased survival of both neurons and satellite cells and the number of proliferating Schwann cells. Immunocytochemistry and immunoblotting revealed that VEGF was expressed in virtually all nerve cells in the SCG but only in a population of small-diameter (<35 micrometers) neurons representing approximately 30% of the neurons in DRG. Immunostaining showed that the VEGF receptor fetal liver kinase receptor (flk-1) was found on nerve cell bodies in DRG and to a lesser extent on neurons in SCG. Growth cones of regenerating axons from both types of ganglia exhibited flk-1 immunoreactivity, as did Schwann cells. We conclude that VEGF has both neurotrophic and mitogenic activity on cells in the peripheral nervous system.

Animals↗

A role of migratory Schwann cells in a conditioning effect of peripheral nerve regeneration.

The common peroneal nerve in mice was conditioned by axotomy around the head of the fibula. At various intervals from 1 day to 2, 3, 5, 15, and 25 days, a test lesion was made by axotomy 15 mm proximal to the conditioning lesion site. The proximal stump of the transected nerve was sandwiched between two sheets of thin plastic film and remained in vivo for various intervals from 3 h to 6, 9, 12, 24, 48, 72 and 96 h. The regenerating axons were visualized on the film with silver nitrate impregnation. Schwann cells were visualized migrating onto the film using immunohistochemistry with anti-S-100. To determine the effects of migratory Schwann cells on axonal outgrowth, a film model was established on one limb. After the nerve stump was removed from the film, the treated film was transferred to a new lesion on the contralateral limb and 2 days later the film was harvested for histological examination. Conditioned by a prior axotomy more than 3 days earlier, regenerating axons sprouted within less than 1 h after the test lesion was established and grew naked at five times higher rate: The growth rate was similar to that observed during regeneration in the presence of migratory Schwann cells (ordinary type). After a short interval, the axons, which had been ensheathed by migratory Schwann cells (reactive type), continued growing at a significantly (P < 0.01) higher rate. The reactive type of cells had fewer numbers of branches and higher activity in promoting axonal outgrowth than the ordinary type. Thus, both ordinary and reactive types of cells played key roles in initiating and maintaining a conditioning effect, respectively.

Animals↗

Spatiotemporal progress of nerve regeneration in a tendon autograft used for bridging a peripheral nerve defect.

We have previously shown that a tendon autograft from the rat tail can support regeneration across a gap in the continuity of the rat sciatic nerve. In this study, we characterized the spatiotemporal progress of regeneration in such a graft bridging a 10-mm defect in the sciatic nerve of the rat. Regeneration was assessed 7, 10, 14, or 18 days postoperatively, by immunocytochemistry for axons, Schwann cells, and macrophages and histochemistry for blood vessels. Axonal regrowth into the grafts showed an initial delay period of 6.8 days, whereafter axons grew at a rate of 1.0 mm/day. Schwann cells grew into the grafts from both the proximal and distal nerve segments, proximally just ahead of the axonal front. Macrophages were initially preferentially located at the periphery of the grafts, but gradually increased inside the grafts. Blood vessels entered the grafts from both the proximal and distal aspects of the severed nerve. The onset of vascularization appeared to coincide with axonal regeneration into the grafts.

Alkaline Phosphatase↗

Bridging defects in nerve continuity: influence of variations in synthetic fiber composition.

Synthetic filaments introduced into a silicone tube may help to enhance axonal growth over extended defects in nerve continuity [1]. Here we test the influence of number (0, 3, 7 or 15), size (diameter 150 or 250 microm) and material of filaments (polyamide or catgut) enclosed in such tubes (inner diameter 1.98 mm) on axonal growth across a 10 mm defect in rat sciatic nerve. The morphology of the tube content was analyzed four weeks post-surgery. The area of the formed tissue matrix inside the tube showed no difference between the groups. Myelinated axons were observed in the formed tissue matrix inbetween and peripheral to the filaments, however, separated from the filaments by concentric cell layers. The number of myelinated axons was less in the tubes with 15 filaments, most pronounced when catgut filaments were used. In most cases, except in tubes with 15 catgut filaments, fibers had grown into the distal nerve segment (pinch reflex test/light microscopy). We conclude that an intrinsic framework consisting of a limited number of synthetic filaments inside an extrinsic framework (silicone tube) does not disturb nerve regeneration. The formed tissue matrix was neither influenced by the presence or the numbers (if less than or equal to seven filaments), type of filaments nor the size of the filaments indicating the importance of the inserted nerve segments.

Journal Article↗

Hearing as substitution for sensation: a new principle for artificial sensibility.

We describe a new principle for artificial sensibility of the hand based on sense substitution, using hearing as substitution for loss of sensation. The experiments were performed on 3 patients who had recently undergone isolated median nerve repair, 1 patient with replantation of an amputated forearm, 1 patient using a myoelectric prosthesis, and 4 patients using cosmetic prostheses. Small condenser microphones were mounted dorsally on the distal phalanges of multiple fingers of the nonsensate hands or prostheses. The friction sound, reflecting the vibrotactile stimuli generated by the moving touch of the objects, was picked up by the microphones and processed in a stereo amplifier that separated signals from individual fingers into different channels. The signals were transmitted to earphones, making possible a spatial resolution that enabled identification of each finger by the generated acoustic stimuli. Since the friction sound is characteristic of specific surfaces and textures, the corresponding acoustic stimuli made possible identification of different textures, such as glass, metal, wood, and paper, without using vision. We conclude that sense substitution using specifically processed acoustic stimuli as a substitute for sensation may represent a useful principle for generation of artificial sensibility in prostheses or hands lacking sensibility due to lesions in the peripheral or central nervous system or because of neurologic disease.

Acoustic Stimulation↗

Neurophysiological findings in vibration-exposed male workers.

Fractionated nerve conduction, vibrotactile sense, and temperature thresholds were studied in 73 symptomatic vibration-exposed male workers. Three symptomatic groups were distinguished: patients with isolated sensorineural symptoms; with isolated vasospastic problems; and with both. Clinical carpal tunnel syndrome occurred in 14 patients and abnormal cold intolerance (without blanching of the fingers) in 23. In the group as a whole, nerve conduction studies were abnormal in the median nerve but not in the ulnar nerve and vibration perception and temperature thresholds were impaired. Of the three symptomatic groups, patients with isolated sensorineural symptoms differed from controls. No differences were seen between patients with and without clinical carpal tunnel syndrome. With severe sensorineural symptoms the vibration perception thresholds, but not the values of the nerve conduction studies, were further impaired. The results indicated two injuries that are easily confused: one at receptor level in the fingertips and one in the carpal tunnel. Careful clinical assessment, neurophysiological testing, and examination of vibrotactile sense are required before carpal tunnel release should be considered in these patients.

Adult↗

Autologous tendons used as grafts for bridging peripheral nerve defects.

This study was performed to investigate whether autologous collagen and other extracellular matrix components could be used in nerve repair by bridging a 10 mm defect in the rat sciatic nerve. Three models of repair were examined. In the first model, a rat tail tendon was teased and subsequently rolled to form a loose collagen roll which was sutured over the defect. In the second model, an intact tendon was used. In the third model, a teased tendon was pretreated with attachment of nerve segments to each end for 4 weeks before grafting. Both teased and intact tendons supported regeneration, to some extent. Pretreatment resulted in migration of Schwann cells into the graft, and enhanced regeneration.

Animals↗

Regeneration of the rat sciatic nerve into allografts made acellular through chemical extraction.

The aim of this study was to develop a procedure by which myelin and Schwann cells could be removed from a peripheral nerve while the basal lamina tubes, remained intact, and to test if such preparations could be used as allografts for the repair of a gap in the continuity of the rat sciatic nerve. We found that extraction with the detergents Triton X-100 and deoxycholate resulted in acellular nerve segments with preserved basal lamina tubes, here defined as the tubes which surrounds the axon/Schwann cell units. The morphology of the acellular nerve segments was revealed by scanning electron microscopy, teasing, immunohistochemistry and electrophoresis. Such grafts when allografted between two outbred rat strains, were found to support outgrowth of axons and migration of Schwann cells, which reoccupied the empty basal lamina tubes without excessive signs of inflammation. This new paradigm offers a possible solution to the major shortcomings of autologous nerve grafts, i.e., the requirement to sacrifice a healthy nerve and the shortage of graft material available for repair.

Animals↗