We have investigated in vitro the release kinetics and bioactivity of fibroblast growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to evaluate the effects of the FGF-2 delivery mechanism on the repair of articular cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in depth, which were too large to undergo spontaneous repair, were created in the femoral trochlea of rabbit knees. These defects were then filled with the sealant. Approximately 50% of the FGF-2 was released from the sealant within 24 hours while its original bioactivity was maintained. The implantation of the fibrin sealant incorporating FGF-2 successfully induced healing of the surface with hyaline cartilage and concomitant repair of the subchondral bone at eight weeks after the creation of the defect. Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans

1. By unilateral resection of the posterior ends of the sixth to eleventh ribs including the costal parts of both costo-vertebral joints, progressive scoliosis can regularly be provoked in young rabbits. Rotation of the vertebrae is prominent in the experimental deformity. 2. Although severe progressive scoliosis can be provoked by a surgical procedure we do not yet know the deforming forces which are released by the operation, but the way lies open for accurate studies on these factors. 3. It seems possible that studies on experimental progressive scoliosis may provide us with new methods to counteract or cure scoliosis in children. The goal is a means to reverse the deforming forces during growth so that the child's spine is straight when growth ceases

In rabbits, repair of incisions in the central part of the meniscus has been demonstrated after surgical excision of the peripheral rim. Healing took place via a highly cellular but relatively avascular fibrous tissue stroma which proliferated from the synovial margin and invaded along the cut edge of the meniscus. Suturing facilitated this healing process by providing stability and possibly by supplying bridges for synovial cells to migrate onto the meniscus. Transformation of fibrous tissue into fibrocartilage has also been observed

1. Stretching of the tibial nerve cut 2 centimetres above the ankle has been the subject of an experimental study in rabbits. 2. The effects on intraneural microcirculation, on vascular permeability, and on the barrier function of the perineurium have been analysed with the aim of determining the extent to which a divided nerve can be stretched without interfering with the process of repair. 3. The results obtained may prove valuable for understanding basic mechanisms and for establishing certain important limitations when end-to-end suture of a nerve trunk is performed under some degree of tension in man

1. A hypothesis outlining an auto-immune mechanism for antibody production against autogenous nucleus pulposus is presented. 2. Auto-antibodies to autogenous nucleus pulposus have been experimentally produced in rabbits. 3. These antibodies are cell-bound within lymphoid cells and are greatest in primary lymph nodes. This antibody is demonstrated by a positive pyronin reaction. 4. Lymphoid cells fixed in Carnoy's fluid and stained for pyronins also show a distinct natural yellow fluorescence. This fluorescence occurs only in the cytoplasm of those cells which are pyronin-positive and presumably producing antibody. 5. The lymph node phase of the reaction is greatest at four days and is sustained for three weeks. A secondary generalised lymph node response occurs in all lymph nodes at six weeks

Aims

Ageing-related incompetence becomes a major hurdle for the clinical translation of adult stem cells in the treatment of osteoarthritis (OA). This study aims to investigate the effect of stepwise preconditioning on cellular behaviours in human mesenchymal stem cells (hMSCs) from ageing patients, and to verify their therapeutic effect in an OA animal model.

The blood supply of the vertebral column of the rabbit has been studied. A description of the embryological development of the blood supply is followed by a description of the blood vessels supplying the adult vertebra

1. Experimental defects in the cranial vaults of young adult rabbits were implanted with decalcified, deproteinised and deep frozen homogenous whole bone. The experiments were similar to those of Ray and Holloway (1957) except that these workers used rats as the experimental animals. In addition, six control defects were made and not implanted. 2. All animals were killed six weeks after operation and thirty-four defects were studied by radiology and by histology. 3. All implants became surrounded by connective tissue and in all cases some new bone formed in apposition to implanted fragments. The degree of incorporation of the implants in new bone varied widely, not only between the three implanted groups, but also within each group. In general, new bone formation was greatest in defects implanted with deproteinised and whole bone, least in defects implanted with decalcified bone. 4. The fate of bone implants and the extent to which they can be said to induce osteogenesis are discussed

Angiogenin, a potent blood vessel inducing protein, was implanted into experimentally injured menisci of 75 New Zealand white rabbits. Localised neovascularisation occurred in 52% of the angiogenin-treated animals, and in 9% of the controls. Neovascularisation induced by angiogenin may enhance healing of injuries within the poorly vascularised meniscal fibrocartilage, and improve the results of meniscal repair

This experiment demonstrates that infiltration of hydrocortisone into rabbit calcaneal tendons has a direct effect on the tendon, producing necrosis of collagen at the site of injection. The repair of the lesion so produced is incomplete even after eight weeks, and is often complicated by dystrophic calcification. Similar morphological changes may account for spontaneous rupture of tendons in patients receiving steroid infiltration

1. A method is described for the in vivo and in vitro study of osteogenesis by implanting a modified transparent chamber in half lop-eared rabbits (as originated by Sandison 1928). This method allows the daily observation and photography of the developing bone and the study of its intimate connection with the vascularity of the area. 2. The osteogenetic potential of a variety of substances can also be investigated by this method. The tissue in the chamber can easily be prepared for its final examination by optical and electron microscopy and by other laboratory techniques

Premature fusion of the triradiate cartilage was obtained surgically in 10 three-week-old rabbits, and compared with isolated fusion of the ilio-ischial and of the ilio-pubic limbs of the triradiate cartilage in two further groups of 10 rabbits. Complete fusion caused acetabular dysplasia five weeks after operation in all animals and hip dislocation at nine weeks in half of them; ilio-ischial fusion had a comparable effect. Ilio-pubic fusion had only a minimal effect on acetabular development. The posterior position of the ilio-ischial limb in the acetabulum and its predominance in the formation of the triradiate cartilage in quadrupeds may have contributed to its decisive effect on acetabular development

Bone apatite contains carbonate and is therefore not pure hydroxyapatite. We have successfully developed sintered carbonate apatite (CA) with a concentration of carbonate of 6 weight% and have evaluated its osteoconductive and bioresorption characteristics. Cylindrical porous sintered CA and sintered hydroxyapatite (HA) measuring 4 × 4 mm with a porosity of 20% were implanted into surgically-created bone defects in the knees of rabbits. The animals were killed after 1, 3, 6 and 12 months. The defects were evaluated by microfocus CT and histology. Bone growth into and around both materials increased. Newly-formed bone was placed in direct contact with both. Osteoclast-like cells resorbed only CA, and were coupled with osteoblasts. The porosity of sintered CA increased, indicating bioresorption, whereas that of sintered HA did not increase. Our findings indicate that sintered CA may be useful as a bioresorbable bone substitute

We performed intra-articular reconstruction of the anterior cruciate ligament (ACL) with the semitendinosus tendon placed in 2 mm diameter tunnels in 21 skeletally immature rabbits. The operation caused 11% damage to the physis of the femur on the frontal plane and 3% of its cross-sectional area but no alteration of growth or axial deviation of the bone resulted. In the tibia, the operation caused 12% damage to the physis in the frontal plane and 4% of the cross-sectional area. Two tibiae developed valgus deformities and one was shortened. Histological examination showed no areas of epiphysiodesis. There was no abnormality of growth-plate thickness in the two cases of tibia valga. Osseous metaplasia in the grafted tendons did not occur. The results suggest the need for careful evaluation of the percentage of damage to the growth plate before using intra-articular methods for reconstruction of the anterior cruciate ligament in adolescents

We compared the effects of continuous passive motion with those of intermittent active motion on the results of the resurfacing with autogenous periosteal grafts of full-thickness defects on the articular surface of rabbit patellae. Of 45 rabbits with defects, 30 received grafts. Fifteen of these had continuous passive motion for two weeks and intermittent active motion for four weeks; the other 15 had intermittent active motion for six weeks. In 15 the defects were not grafted (control group) and they had intermittent active motion for six weeks. Ten more rabbits had a sham operation. Six weeks after surgery, the results were assessed by the gross appearance, histology, histochemistry, immunohistochemistry and electron microscopy. By all assessments the quality of neochondrogenesis produced by periosteal grafts was superior to that in ungrafted defects (p less than 0.05) and the results in continuous passive motion treated animals were superior to those in intermittent active motion treated animals (p less than 0.05). The periosteal grafts produced hyaline cartilage containing type II collagen but the organisation of its fibres was irregular

We implanted cylinders of cobalt-chrome or titanium, with smooth or porous surfaces, into rabbit bones which had been inoculated with suspensions of Staphylococcus aureus in various doses. The bacterial concentration required to produce infection of porous-coated titanium implants was 2.5 times smaller than that necessary to infect implants with polished surfaces. Porous-coated cobalt-chromium implants required bacterial concentrations that were 40 times smaller than those needed to infect implants with polished surfaces, and 15 times smaller than those required to infect porous-coated titanium implants. The other advantages and disadvantages of the various implants, such as improved osseointegration, larger ion-release surfaces, surface wear and relative stiffness, must be weighed against the higher infection rates in the porous-coated implants, and particularly in the cobalt-chromium implants

In an attempt to explain the distribution of lesions of caisson disease of bone in the human femur, the regional distribution of circulating microspheres which had been labelled with scandium-46 was studies in the femur of the rabbit. Microspheres with a diameter of 15 microns were equally distributed between the two ends of the bone and between the upper and lower halves of the shaft. However, microspheres with a diameter of 50 microns congregated in the upper end of the femur and in the lower half of the shaft, the two sites most commonly affected by caisson disease. A large percentage of the microspheres in the shaft, especially the larger spheres, were retained in the marrow. It is suggested that the microcirculation of the marrow may act as a filter and that the nature and distribution of its vessels determine the site of impaction of circulating emboli. This would explain why lesions of the shaft mainly affect the medulla of the bone and not the cortex

Intra-osseous phlebography and the measurement of intramedullary pressure (IMP) have been used clinically and in experimental animals as qualitative methods of measuring blood flow in the bone. The normal phlebographic appearances in long bones are not clearly understood and the correlation between these appearances and the IMP is not known. The distal femora of 10 anaesthetised rabbits were cannulated percutaneously. The IMP was measured and phlebography performed by injecting a radio-opaque dye (Conray 280).The mean resting IMP was 33 millimetres of mercury with a range of 7 to 81 millimetres of mercury. The rate of elimination of dye from the marrow varied from less than 1 minute to 40 minutes. There was no correlation between the rate of elimination of dye and the IMP. Variation in the medullary phlebographic appearance and in the routes of drainage were noted. We concluded that the wide range of resting values for both techniques suggest that neither is a true measure of blood flow in the bone and that the results of research or clinical investigation using these techniques should be viewed with caution

We carried out limb lengthening in rabbits and then transplanted osteoblast-like cells derived from the tibial periosteum to the centres of distracted callus immediately after distraction had been terminated. Two weeks later the transaxial area ratio at the centre of the distracted callus and the bone mineral density (BMD) were significantly higher in the transplanted group, by 21% and 42%, respectively, than in the non-injected group or the group injected with physiological saline (p < 0.05). Callus BMD as a percentage of density in uninvolved bone was also significantly higher in the transplanted group (p < 0.05) than in the other two groups, by 27% and 20% in the second and fourth weeks, respectively (p < 0.05). Mechanically, the callus in the transplanted group tended to be stronger as shown by the three-point bending test although the difference in fracture strength was not statistically significant. Our results show that transplantation of osteoblast-like cells promotes maturity of the distracted callus as observed at the second and fourth weeks after lengthening. The method appears promising as a means of shortening the consolidation period of callus distraction and decreasing complications during limb lengthening with an external fixator

Subtotal synovectomy was performed in the knee joints of New Zealand white rabbits. The changes noted in the articular cartilage as manifest by decreased metachromatic staining of the matrix were considered to indicate matrix degradation caused by the altered joint environment. The documentation of the enzyme changes suggests that the histological alteration in the articular cartilage noted after synovectomy may be mediated through the activation of endogenous chondrocyte lysozomal enzymes, particularly cathepsin and acid hydrolases