1. The results of the present investigation indicate that in the foetal rat the juxta-epiphysial vascular bed consists of a dense irregular network of sinusoids in direct contact with the growth cartilage, supplied by end-arteries, and drained by a profusion of metaphysial sinusoids. 2. The circulation is a closed one–that is, the endothelium is unbroken in its continuity and microhaemorrhages do not occur against the cartilage. 3. It is possible that juxta-epiphysial endothelial cells or their derivatives are chondrolytic, and that they participate directly, together with other mesenchymal derivatives, in the removal of cartilage as a preparatory stage in enchondral bone formation

We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential

1. The pattern of tritiated thymidine labelling in the cells of the epiphysial cartilage and metaphysis of the tibia in the rat is described for intervals of one hour to twenty-eight days after injection. 2. The region of dividing cells is defined and evidence given for a zone of reserve cells at the top of the cartilage columns. 3. The difficulties of quantitative grain count studies are discussed, and some approximate values are given for the generation time and mitotic cycle periods of the cartilage plate cells. 4. Some further evidence is given about the life cycles of the osteoblast and the osteoclast

We studied the calcium content and mechanical strength of cortical bone from rats and dogs after different periods of demineralisation, showing that the rate of demineralisation differed considerably between the species. Specimens from the rat were further treated by chemical extraction and autolysis and tested for osteoinductive properties. We showed that partially demineralised cortical bone retained adequate mechanical strength, while retaining the biological effects of completely demineralised bone. This shows that it is possible to prepare allografts which have adequate mechanical strength and still retain osteo-inductive properties

Spinal nerve roots often sustain compression injuries. We used a Wistar rat model of the cauda equina syndrome to investigate such injuries. Rapid transient compression of the cauda equina was produced using a balloon catheter. The results were assessed by daily neurological examination and somatosensory evoked potential (SEP) recording before surgery and ten weeks after decompression. Compression of the spinal nerves induced changes in the SEP which persisted for up to ten weeks after decompression, but it had no effect on the final neurological outcome. Our study shows the importance of early surgical decompression for cauda equina syndrome

A stump neuroma is caused by the disorganised growth of axon cylinders into proliferating granulation tissue, but this is stopped by an undamaged epineural sleeve. We report experiments in the rat in which the epineural sleeve of the stump of the sciatic nerve was freed from nerve fascicles for about 5 mm and then sealed with a synthetic tissue adhesive. Neuroma formation was largely prevented in comparison with the results of other methods. This new technique has been used to treat 68 painful neuromas in 36 patients. All but three of the patients were cured or improved and none were made worse

Aims

Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD.

Based on a study using a retrograde neurotracer, we have previously found that the dorsal portion of the L5/6 disc in the rat is multisegmentally innervated by dorsal root ganglia (DRG) from the level of T13 to L6, and that sensory nerve fibres from DRG of T13, L1 and L2 pass through the paravertebral sympathetic trunks. In this study in newborn rats, we injected crystals of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylinedocarbocyanine perchlorate (DiI) into the DRG of T13, L1 and L2 and showed DiI-labelled sensory nerve fibres in the dorsal portion of the discs from the level of T13/L1 to L5/6. Our results show that the dorsal portion of the lumbar discs is innervated by the DRG from levels T13 to L2

Ischaemic preconditioning is a process by which exposure of a tissue to a short period of non-damaging ischaemic stress leads to resistance to the deleterious effects of a subsequent prolonged ischaemic stress. It has been extensively described in the heart, but few studies have examined the possibility that it can occur in skeletal muscle. We have used a rat model of ischaemia of one limb to examine this possibility. Exposure of the hind limb to a period of ischaemia of five minutes and reperfusion for five minutes significantly protected the tibialis anterior muscle against the structural damage induced by a subsequent period of limb ischaemia for four hours and reperfusion for one hour. This protection was evident on examination of the muscle by both light and electron microscopy. Longer or shorter times of prior ischaemia had no effect

1. Decalcified lyophilised rat bone matrix prepared by Urist's method acts as an inductor of cartilage and bone when implanted into animals of other species, namely mice, rabbits and gerbils. Induction in rabbits and gerbils was very much weaker than in the mouse. 2. The site of implantation affected the outcome; intramuscular implants induced cartilage and bone more strongly and regularly than subcutaneous or intraperitoneal implants. 3. Rabbit transitional epithelium, growing in cortisone-treated gerbils, caused bone induction, but in general, results with this species suggest that it responds poorly to bone-inducing stimuli. 4. Cortisone, used as an immunosuppressant, did not inhibit bone and cartilage induction

Synthetic bone substitutes provide an alternative to autograft but do not give equivalent clinical results. Their performance may be enhanced by adding osteogenic growth factors. In this study, TGFβ1 was absorbed on to a carrier of β tricalcium phosphate and Gelfoam® and used to fill a defect around a tibial implant in a rat model of revision arthoplasty. We added 0.0, 0.02 μg, 0.1 μg or 1.0 μg of TGFβ1 to the carrier and then implanted it around an hydroxyapatite-coated stainless-steel pin in the proximal tibia of rats. The tibiae were harvested at three, six or 26 weeks and the amount of bone formation and ceramic resorption were assessed. TGFβ1 had no effect on the amount of bone in the defect, the amount of fluorescent label incorporated or the rate of mineral apposition. The growth factor did not significantly affect the amount of β TCP remaining in the tissue at any of the time points

1. An apparatus was designed to determine the shearing strength of the upper tibial epiphysis in the rat. Observations were made with this instrumenton normal animals, on animals receiving growth-hormone, and on animals receiving oestrogen. 2. When the epiphysis separates from the diaphysis, the plane of cleavage is constant, passing through the third layer of the epiphysial plate. 3. Growth-hormone decreases and sex-hormone increases the shearing strength of the epiphysial plate. These changes are due to alterations produced by these two hormones in the thickness of the third layer of the epiphysial plate. 4. It is suggested that these findings may be of significance in providing an anatomical basis for slipping of the upper femoral epiphysis in man, especially when it is associated with the adiposo-genital syndrome or with rapid adolescent growth

Using a rat model, we created a bone-to-titanium interface and applied phagocytosable high-density polyethylene pArticles between the bone and implant, either initially or when the interface had matured. No fibrous membrane developed and no bone resorption was found. If sliding movements were initiated at the interface after two weeks, there was formation of a fibrous membrane. The additional application of pArticles did not change the thickness of the membrane, and there were only minor qualitative changes. Creation of a membrane by movement followed by cessation of movement and the application of pArticles caused the membrane to persist, whereas in a pArticle-free control group bone-to-metal contact was re-established. Our findings suggest that mechanical stimuli are of primary importance for prosthetic loosening, and that pArticles may modulate the later stages of the loosening process

Our aim was to develop a clinically relevant model of atrophic nonunion in the rat to test the hypothesis that the vessel density of atrophic nonunion reaches that of normal healing bone, but at a later time-point. Atrophic nonunion is usually attributed to impaired blood supply and is poorly understood. We determined the number of blood vessels at the site of an osteotomy using immunolocalisation techniques in both normally healing bones and in atrophic nonunion. At one week after operation there were significantly fewer blood vessels in the nonunion group than in the healing group. By eight weeks, the number in the atrophic nonunion group had reached the same level as that in the healing group. Our findings suggest that the number of blood vessels in atrophic nonunion reaches the same level as that in healing bone, but at a later time-point. Diminished vascularity within the first three weeks, but not at a later time-point, may prevent fractures from uniting

Little is known about the tissue reactions to various implant materials which coincide with an inflammatory reaction. We used the avridine arthritis rat model to evaluate the tissue response in the synovial, interstitial and subcutaneous tissues after implant insertion. Quantitative immunohistochemistry showed that normal joint synovial tissue is dominated by ED2-positive resident macrophages. Polyethylene implants induced a much stronger foreign-body reaction than titanium implants, as measured by the number of interfacial ED1-positive macrophages. The tissue response to titanium and polyethylene was also vastly different in arthritic synovial tissue compared with control tissue. It is likely that these biomaterials interact differently with inflammatory cells or intermediary compounds. It may be that arthritic synovial tissue produces reactive oxygen intermediates (free radicals) with which titanium has a unique anti-inflammatory interaction in vitro

Compartment syndrome is a unique form of ischaemia of skeletal muscle which occurs despite patency of the large vessels. Decompression allows the influx of activated leucocytes which cause further injury. Vitamin C is a powerful antioxidant which concentrates preferentially in leucocytes and attenuates reperfusion-induced muscle injury. We have evaluated the use of pretreatment with oral vitamin C in the prevention of injury caused by compartment syndrome in a rat cremasteric muscle model. Acute and delayed effects of pretreatment with vitamin C were assessed at one and 24 hours after decompression of compartment syndrome. Muscle function was assessed electrophysiologically. Vascular, cellular and tissue inflammation was assessed by staining of intercellular adhesion molecule-1 (ICAM-1) and by determination of the activity of myeloperoxidase (MPO) in neutrophils and tissue oedema. Compartment syndrome impaired skeletal muscle function and increased the expression of ICAM-1, activity of MPO and muscle weight increased significantly. Pretreatment with vitamin C preserved muscle function and reduced the expression of ICAM-1, infiltration of the neutrophils and oedema

1. The process of repair after fracture of the humerus of the growing rat has been studied by histological, histochemical and biochemical methods. 2. Both periosteal and surrounding mesenchymal cells take part in the process of repair. 3. The primary framework of collagen bridging the gap is mainly formed by the mesenchymal cells, while calcification and ossification of the framework is largely a function of the periosteum. 4. The mucopolysaccharide content rises rapidly in the first week after injury, and is followed by a rise in the collagen content during the second week. The deposition of calcium phosphate during the third and fourth weeks causes an apparent fall in the collagen content during that period. The collagen content tends to return to normal during the phase of remodelling in the fifth and sixth weeks. 5. The tensile strength of the healing bone bears a close relation to its collagen content

Immobilisation causes denervation-like changes in the motor endplates, decreases the content of IGF-I, and increases the number of IGF-I receptors in the spinal cord. In the rat we investigated whether similar changes occur after a fracture of the midshaft of the femur which had been treated by intramedullary fixation with adequate or undersized pins. A more pronounced reduction in muscle wet weight was seen after fixation by undersized pins as well as decreased ash density of the ipsilateral tibia which did not completely return to normal within the 12-week experimental period. The nicotinic cholinergic receptors in the motor endplates of tibialis anterior were increased (p < 0.01) and there was a significant increase (p < 0.02) in IGF-I receptors in the lumbar spinal cord ipsilateral to the fracture after treatment by undersized nails. These changes may be associated with the impaired proprioception, co-ordination and motor activity which are sometimes seen after fractures

An orientated substratum has been implicated in the development and regeneration of axons and synapses. We prepared a basement membrane matrix from autogenous striated muscle, used it to repair the sciatic nerve in rats, then investigated the results by histology and electrophysiology. When treated grafts were coaxially aligned with the nerve fascicles functional recovery appeared within 30 days, with good growth of axons into the distal nerve. Grafts with myotubes at right angles to the nerve fascicles supported nerve regeneration but at a slower rate. Grafts of coaxially aligned but untreated muscle allowed axon penetration only through naturally degenerated muscle fibres, with minimal axon penetration of the distal nerve. It is concluded that in the rat a treated graft with correctly orientated empty myotubes can facilitate and guide the regeneration of peripheral nerve after injury and so lead to recolonisation of the distal stump with functional recovery

A model of tourniquet ischaemia was developed in the hind limb of the rat, and the metabolic changes that occurred in the calf muscles were monitored by the non-invasive technique of phosphorus-31 nuclear magnetic resonance spectroscopy. During ischaemia the intramyocellular pH became acidic as the level of phosphocreatine declined and that of inorganic phosphate rose. Phosphocreatine was no longer detectable after approximately 2 hours and ATP was depleted after approximately 3.5 hours. Metabolic recovery was rapid (1 hour) if ATP was present when the tourniquet was released but was prolonged (3 or more hours) if ATP was depleted. Hourly release of the tourniquet for 10 minutes ensured the maintenance of ATP and rapid metabolic recovery. Release for intervals of only 5 minutes did not have the same protective effect and in fact worsened tissue pH during the period of tourniquet ischaemia. Heparin and corticosteroids were without effect during and after periods of tourniquet ischaemia