Ischaemia kills osteocytes, but opinions differ as to how long they can survive. These differences are due to the varying methods of inducing ischaemia, and to the different criteria for diagnosing cell death. Using rabbit bone and a technique of in vitro ischaemia at 37 degrees C, we have shown by electron microscopy that, after up to two hours, the changes which occur are probably reversible; after four hours, the cells were irreversibly damaged. This difference could not be detected by light microscopy. After 24 hours of ischaemia, most lacunae were empty or contained only osteocyte debris. We conclude that osteocytes suffer irreversible damage after in vitro ischaemia of about two hours, which is much the same response as that of most other mammalian cells

Our aim was to investigate vascular endothelial growth factor (VEGF) expression after lacerations of a meniscus in a rabbit model. Specimens of meniscus were examined using immunohistochemistry, enzyme-linked immunoassay and the reverse transcription polymerase chain reaction after one, two, five or ten weeks. In the periphery of the meniscus 90% of the lacerations had healed after five and ten weeks, but no healing was observed in the avascular area. Expression of VEGF protein and VEGF mRNA was found in the meniscus of both the operated and the contralateral sites but both were absent in control rabbits which had not undergone operation. The highest expression of VEGF was found in the avascular area after one week (p < 0.001). It then lessened at both the vascular and avascular areas, but still remained greater in comparison with the control meniscus (p < 0.05). Despite greater expression of VEGF, angiogenesis failed at the inner portion. These findings demonstrated the poor healing response in the avascular area which may not be caused by an intrinsic cellular insufficiency to stimulate angiogenesis

The paper reports an experimental investigation into the mechanisms whereby the joints of living animals maintain their precise contours. The normal patter of joint incongruity in the rabbit's hip having first been established, three groups of experimental animals underwent operative procedures designed to reduce the joint pressure to a level unrealistic in normal life. In one group the hip was dislocated by manipulation; in a second group the muscles around the hip joint were divided; and in a third group the hind limb was disarticulated through the knee. When the animals were killed at intervals of a few weeks after the operations the experimental hip joint showed increased congruity in all cases. It is concluded that in immature animals there is a mechanism in joints to control the modelling of their shapes towards an ideal incongruity, and that that mechanisms is pressure sensitive

1. Synovitis was induced in the hip joints of fifty-six rabbits by the intra-articular injection of surgical talc. The opposite hip joint and eleven suitable"sham" operations served as controls. 2. The results in the hips injected with talc were as follows. Widening of the medial joint space and sometimes acetabular changes were seen; enlargement of the femoral head and neck in two planes was found, with, in most cases, flattening of the superior aspect of the head; there was thickening of the joint cartilage and sometimes deformity of the capital epiphysis; thickening of the cartilage was the main cause of the coxa magna, cervix magna and ischium magnum. 3. The embryology, micro-anatomy and development of the hip joint is reviewed and attention is drawn to the configuration of the layers of germinal cartilage cells. The effect of an induced synovitis in producing hyperplasia of the joint cartilage, incongruity of the articulating surfaces and subsequent subluxation is discussed

We have developed a novel, two-layered, collagen matrix seeded with chondrocytes for repair of articular cartilage. It consists of a dense collagen layer which is in contact with bone and a porous matrix to support the seeded chondrocytes. The matrices were implanted in rabbit femoral trochleas for up to 24 weeks. The control groups received either a matrix without cells or no implant. The best histological repair was seen with cell-seeded implants. The permeability and glycosaminoglycan content of both implant groups were nearly normal, but were significantly less in tissue from empty defects. The type-II collagen content of the seeded implants was normal. For unseeded implants it was 74.3% of the normal and for empty defects only 20%. The current treatments for articular injury often result in a fibrous repair which deteriorates with time. This bilayer implant allowed sustained hyaline-like repair of articular defects during the entire six-month period of observation

Aims

To evaluate graft healing of decellularized porcine superflexor tendon (pSFT) xenograft in an ovine anterior cruciate ligament (ACL) reconstruction model using two femoral fixation devices. Also, to determine if pSFT allows functional recovery of gait as compared with the preoperative measurements.

Our purpose was to determine whether continuous passive motion enhanced the quality of knee ligament reconstruction using carbon fibre. In 46 rabbits the medial collateral ligaments were excised and replaced with carbon fibre prostheses. The animals were treated postoperatively by either continuous passive motion, cast immobilisation or cage activity, termed intermittent active motion. At six weeks, the ligaments were compared histologically and biomechanically with normal (control) medial collateral ligaments and with sham-operated controls. The ligaments treated with continuous passive motion were superior to those in the other two treatment groups. There were no ligament failures in any of the groups. This study suggests that continuous passive motion, initiated immediately postoperatively, enhances the biomechanical properties of carbon fibre ligament replacement of the medial collateral ligament while preventing the harmful effects of joint immobilisation

A longitudinal incision resembling a bucket-handle tear was made in the menisci of 8 rabbits, 6 dogs, 11 pigs and 12 sheep. In some of the animals of each species the cut was repaired by suturing, and in others it was not. Gross inspection, as well as examination by light and electron microscopy, showed that no healing had occurred after six months in the sutured or the unsutured wounds and that the meniscus was incapable of significant intrinsic repair. In a second experiment longitudinal, transverse and T-shaped cuts were made in the menisci of 12 sheep, and a flap of synovium was sutured into the wound. Three months later there was clear evidence of healing by the formation of cartilaginous tissue. Examination by light and electron microscopy showed that the newly formed repair tissue, possibly derived by metaplasia from the synovium, had a morphology intermediate between hyaline cartilage and fibrocartilage. Synovial implantation may therefore be considered as an alternative to meniscectomy in the management of the torn meniscus

The relationship between the route of inoculation, the dose of inoculum and the development of infection after prosthetic replacement has been determined in an animal model. The rabbit hip served as the model and a Staphylococcus aureus isolated from an infected human hip arthroplasty was introduced using different protocols. The 50% infective dose (ID50) was determined for comparative purposes. Contamination of the wound site with only a few bacteria was likely to result in infection. It was considerably more difficult to induce infection when the operation was performed without inserting the prosthesis, which suggests that the implant inhibits the body's mechanism for dealing with the insult. It was difficult to produce infection by inoculating the organisms into the bloodstream: if this inoculation was delayed till three weeks after operation the animals were often grossly septicaemic by the time the arthroplasty was infected. The results emphasise the importance of minimising intra-operative contamination and the efficacy of antibiotic cover

Demineralised homologous bone-matrix implant was used to bridge a large circumferential osteoperiosteal gap in the diaphysis of the ulna of rabbits. Periodic observations of the graft were made clinically, radiologically, histologically and by tetracycline fluorescence up to forty-two weeks. By the twelfth week after operation 81 per cent of the animals revealed bone formation in the implant and complete bridging of the gap. The new bone was laid on the surface and in the substance of the matrix, suggesting that the inductive principle was acting locally. The bone, once formed, remodelled to the texture of a mature tubular bone and did not undergo absorption during a long follow-up period. Demineralise bone-matrix proved to be a highly osteoinductive and readily osteoconductive material. The graft did not evoke any appreciable local foreign-body or immunogenic reaction. The high degree of success in bridging massive bone defects justifies further serious studies and hopes for a useful substitute for massive autologous bone grafts

1. Experiments are described in which total infarction of the epiphysis was produced in the metatarsal bones of growing rabbits. 2. After operation both proliferation and normal maturation of the cells of the growth plate were slowed or stopped. Cartilage destruction on the metaphysial side of the growth cartilage continued with consequent thinning of the cartilage. Localised areas of cell death appeared in the growth cartilage as early as the second day after operation. These increased in size and led to revascularisation of the epiphysis by metaphysial vessels which grew through the growth cartilage, reaching the epiphysis seven days after operation. The main, central part of the growth cartilage survived intact and its normal structure was restored after epiphysial revascularisation took place. Vessels growing into the bone from outside also contributed to revascularisation of the epiphysis. After revascularisation occurred, new bone formation led to increased radiographic density of the epiphysis

We describe a new method of biological repair of osteochondral defects. In rabbit knees an osteochondral defect was reconstructed with a callo-osseous graft made of a superficial sheet of medullary fracture callus attached to a base of cancellous bone. This was taken from the iliac bone of the same animal which had been osteotomised ten days earlier. The reparative tissues were evaluated for 24 weeks by quantitative histology, biochemical analysis of the uronic acid content, and immunohistochemical staining of collagen constituents. The callo-osseous graft provided significantly faster and better repair of the articular surface than an untreated defect or a callo-osseous graft in which the cells had been devitalised by irradiation before transplantation. Our findings indicate that the callo-osseous graft contributes to the repair process by providing both favourable extracellular matrices and pluripotential mesenchymal cells. Our study tested the hypothesis that early medullary callus generates hyaline cartilage instead of bone after transfer to an articular surface

This paper examines the fate of decalcified allografts (homografts) of iliac cancellous bone impregnated with autologous red marrow and implanted intermuscularly into the anterior abdominal wall of rabbits. In contrast to the findings of Urist and other workers that cortical bone decalcified with hydrochloric acid (HCl) and then freeze-dried is inductive to new bone formation in various heterotopic sites, evidence is presented that iliac bone decalcified by HCl and grafted alone to a muscular site is itself very weakly inductive to bone formation. However, when combined with autologous bone marrow the HCl-decalcified bone provides a better substrate for bone formation by marrow cells than does either undecalcified iliac bone, or iliac bone decalcified with ethylene-diamine-tetra-acetic acid. The freezing or freeze-drying of decalcified bone does not affect new bone formation when implanted alone or with autologous marrow. The differences between the cortical and cancellous bone as inductive substrates for osteogenesis are discussed and the interrelationship of bone and marrow in combined bone grafts are re-evaluated

Little is known of the effects of synovectomy on articular cartilage. In order to investigate this matter, anterior synovectomy of the knee was performed in thirty-five normal adult rabbits and in thirty-five which were given 25 milligrams of hydrocortisone intramuscularly each week afterwards. The animals were killed at intervals from four to 110 days after synovectomy. Histological examination of the regenerating synovium in both groups showed complete structural and functional regeneration by eighty days in the first group and a delay in regeneration in the steroid group. . 35. Sulphur autoradiographs of the articular cartilage of femoral and tibial condyles revealed surface fibrillation and chondrocyte death in 23 per cent of normal knees after eighty days but only 1·8 per cent of knees of animals receiving hydrocortisone. Thus synovectomy in a healthy joint may have an unfavourable effect on the physiology of cartilage by alteration of synovial composition and hyaluronate content in normal joints. Systemically-administered hydrocortisone may reduce this harmful effect in normal cartilage

1. Diametric growth and organisation of the epiphysial cartilage plate have been studied by microradiography of human bone and autoradiography of the epiphysial plate in growing rabbits, using sulphur. 35. These investigations were supplemented by a radiographic study of four patients with dyschondroplasia in whom the progress of the characteristic epiphysial defects were traced during several years' growth. 2. A perichondrial sheath of bone, at the junction of the epiphysial plate with the metaphysis, was demonstrated by microradiography of the distal end of the human femur. Its relationship to epiphysial growth is discussed. 3. Autoradiography, to determine the direction of the cellular proliferation between the epiphysial plate and the overlying perichondrium, demonstrated the appearance of new cartilage cells at the periphery of the plate over a period of six days. 4. The evidence presented strongly favours the postulate that the transverse diameter of the epiphysial cartilage plate increases by appositional growth from the overlying perichondrium and that the same source is responsible for lateral extension of the articular cartilage during growth

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum. We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good. Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results

Objectives

Mesenchymal stem cells (MSCs) are of growing interest in terms of bone regeneration. Most preclinical trials utilize bone-marrow-derived mesenchymal stem cells (bMSCs), although this is not without isolation and expansion difficulties. The aim of this study was: to compare the characteristics of bMSCs and adipose-derived mesenchymal stem cells (AdMSCs) from juvenile, adult, and ovarectomized (OVX) rats; and to assess the effect of human parathyroid hormone (hPTH) 1-34 on their osteogenic potential and migration to stromal cell-derived factor-1 (SDF-1).

We used a rabbit model to investigate the mechanism by which the angulation of fractures is corrected in children. We produced a transverse proximal tibial fracture in one leg of 12 eight-week-old New Zealand white rabbits and measured bone alignment and length and the patterns of bone growth and remodelling. The angle between the joint surfaces changed rapidly to correct the alignment of the limb as a result of asymmetrical growth of epiphyseal plates. In an adult with closed plates, the angle between the joint surfaces cannot therefore improve. The angle at the fracture itself showed slow improvement because of bone drift and the asymmetrical growth of the epiphyseal plates. Remodelling corrected the shape of the bone in the region of the fracture. Periosteal division on the convex side increased the growth of the epiphyseal plate on that side, thus slowing the correction. The effect was relatively small, providing an indication that factors other than the periosteum are important in inducing correction. External torsional deformities developed because of helical growth at the plate. This was probably caused by abnormal posture which induced a torque at the growth plate. Helical growth is the mechanism by which rotational deformities can occur and correct

A clay containing hydroxyapatite (HA) was developed for use as a filling material between an uncemented implant and bone. It consists of 55% HA granules greater than 0.1 mm in size with a homogeneous pore distribution and a porosity of 35% to 48% in a saline solution of sodium alginate (6%). Ti-6A1-4V alloy rods with smooth surfaces were implanted into the distal medullary canal of one osteotomised tibia of 32 Japanese white rabbits. Sixteen rods were inserted with HA clay and 16 without the clay to act as a control group. Six of each group were killed at one week and ten at 12 weeks postoperatively. The pull-out strength of the implants with HA clay was significantly greater at 12 weeks (p < 0.05), as was the percentage of the area of the new bone (p < 0.05). The study suggests that HA clay has an osteoconductive property, allowing adequate bone fixation across a gap at an early stage. The use of HA clay to enhance the early stability of uncemented components may help to improve the functional outcome of total joint arthroplasty

1. The rates of vascularisation in 119 autogenous, homogenous and heterogenous bone grafts, placed in the femoral medullary cavity and under the renal capsule of rabbits, were studied. 2. Substantial differences have been found in the speed of vascular penetration and arrangement among autografts, homografts and heterografts : penetration of the heterogenous implant was six or more times slower. Moreover, large areas of the homografts and heterografts were often totally excluded from the circulation for as long as the research was continued (up to three months). Revascularisation of the cortical bone was slower and less profuse than in cancellous bone, keeping always the same respective proportion between the three types of bone we have described. The results on the kidney were much less constant, and I attribute this to the vascular peculiarities of the bed. 3. Vascular patterns peculiar to the time of implantation and type of graft are described. 4. Suggestive, even if not totally convincing, evidence was found of recanalisation of old vessels inside the graft by advancing vessels from the bed. 5. There is striking correlation between the rate of vascular penetration of the bone implants and their ultimate "take" or incorporation in the bed