We have investigated the changes in the interposed capsule after a Chiari pelvic osteotomy, in an experimental study on dysplastic hips in 20 adolescent rabbits. Radiographic, macroscopic and microscopic observations were made up to 12 months after operation. The new acetabular roof had incorporated the interposed capsule and remodelled completely by six months. By 12 months there was a new, stable hip with continuity between the capsule and the original acetabular cartilage. Histologically, the capsule underwent metaplastic change to fibrocartilaginous tissue after six months, with some hyaline-like cartilage near the joint surface. These changes in the interposed capsule play an important role in the formation of a new joint after a Chiari pelvic osteotomy

The release of prostaglandins E and F from the tibiae of rabbits and the surrounding muscle in vitro after fracture and pinning, or pinning alone, has been compared to the release from unoperated tissues. The fractured tibiae released significantly more prostaglandins E and F than the control tibiae three to 14 days after operation. The pinned tibiae also released more of the two prostaglandins, although this was significant only after 14 days. Consequently it was only around the third day that the fractured tibiae released significantly more prostaglandin E than the tibiae which had been pinned, but not fractured. Similar results were obtained for the release from the muscles surrounding the tibiae. Prostaglandins are important mediators of inflammation as well as potent stimulators of bone resorption. Their increased formation in response to fracture and pinning may stimulate the vascular changes, bone resorption and the proliferation of osteogenic cells observed after trauma to bone

We subjected the proximal tibial growth plates of six-week-old rabbits to either compression or distraction of 1 kg on both legs. On one side the proximal tibial periosteum was divided circumferentially and stripped for 1 cm. After six weeks, growth was measured at both proximal and distal growth plates. Compression inhibited total tibial growth and distraction enhanced it. The compressed growth plate grew less and the distracted growth plate grew more, but there was a reciprocal change at the other end of the bone. Periosteal division enhanced growth at the adjacent growth plate but inhibited it distally; the effect of distraction was enhanced and that of compression reduced. We found reciprocal growth rates at the proximal and distal growth plates. Relatively small amounts of compression or distraction did affect total bone growth. Periosteal division appeared to induce overgrowth at least partly by a mechanical effect; it may be useful as an adjunct to other methods of leg lengthening, though not to epiphyseolysis

Tibial grafts in rabbits were studied using a microscopic technique in vivo that made it possible to photograph the "graft to be" at the donor site and then subsequently to observe the same graft repeatedly at the host site. With this method the effects on the graft tissues of varying degrees of surgical trauma have been tested. The period of follow-up ranged between 14 and 300 days. The grafts removed with minimal trauma showed a more rapid rapid of revascularisation. In this group the first vessels appeared on average seven days after grafting, whereas they took 15 days in the grafts which were more severely traumatised. Bone remodelling started when the vascular density resembled the more pattern and this occurred earlier and much more rapidly in the minimally injured grafts. It correlated with the presence of surviving cells, as shown by histochemical tests, and a causal relationship is suggested. It is concluded that control of trauma is important not only in the preparation of the host bed but also in procurement of the graft. Suggestions are given on techniques to minimise the surgical trauma

Damage to articular cartilage is a common injury, for which there is no effective treatment. Our aims were to investigate the temporal sequence of the repair of articular cartilage and to define a critical-size defect. Full-thickness defects were made in adult male New Zealand white rabbits. The diameter (1 to 4 mm) of the defects was varied in order to determine the effect that the size and depth of the defect had on its healing. The defects were made in the femoral groove of the knee with one defect per knee and eight knees per group. The tissues were fixed in formalin at days 3, 7, 14, 21, 28, 42, 84 and 126 after operation and the sections stained with Toluidine Blue. These were then examined and evaluated for several parameters including the degree of metachromasia and the amount of subchondral bone which had reformed in the defect. The defects had a characteristic pattern of healing which differed at different days and for different sizes of defect. Specifically, the defects of 1 mm first peaked in terms of metachromasia at day 21, those of 2 mm at day 28, followed by defects of 3 mm and 4 mm. The healing of the subchondral bone was slowest in defects of 1 mm

1. Hitherto, no study has been reported on the relative quantitative contributions of blood supply by the different arterial systems of long bone. This paper is a report on such a study in the young adult rabbit. 2. The rates and regional distributions of the blood supply of the nutrient as well as other arteries of the femur were studied after ligation of the nutrient artery. The average rates of reduction in blood flow per minute for the first five minutes through the entire femur as well as the shaft, and the epiphysis and metaphysis on each end, were measured and analysed. The bone blood flow was measured by the method of bone clearance of blood strontium 85. 3. The normal average rate of blood flow through the femurs of average weight of 9·38 grammes was 0·90±0·05 millilitres per minute, or 9·60±0·47 millilitres per minute per 100 grammes of bone. 4. The nutrient artery contributed at least 46 per cent of the normal total blood supply of the entire femur and at least 71 per cent of the normal total blood flow of the shaft including its marrow, and 37 per cent and 33 per cent of the normal total blood flow of the upper and the lower epiphysial and metaphysial areas respectively. 5. About 63 per cent, 30 per cent and 67 per cent of the total normal blood flow through the upper epiphysis and metaphysis, the shaft and the lower epiphysis and metaphysis respectively are still intact in the first five minutes after ligation of the nutrient artery, which represent the approximate proportions of the blood supply by the other regional arteries. 6. These quantitative data obtained in this study offer good support to the qualitative observations made by many previous workers

Any operation involving the implantation of a foreign body increases the risk of infection. The implant material and its surface, the dead space, and any necrosis or vascular changes play a significant role in susceptibility to infection. We investigated the effect of the dead space in an intramedullary nail on the rate of local infection. We inoculated the intramedullary cavities of rabbit tibiae with various concentrations of a human pathogen, of Staphylococcus aureus strain, and then inserted either a solid or a hollow slotted stainless-steel nail. We found a significantly higher rate of infection after use of the slotted nail (59%) than after the solid nail (27%) (p < 0.05)

Ischaemia resulting from increased joint pressure may play a role in the pathogenesis of necrosis of the femoral head epiphysis. We studied the effect of temporary vascular occlusion on this epiphysis in young rabbits. Occlusion for six hours resulted in necrosis of trabecular bone and of intertrabecular marrow and vascular tissue, later followed by revascularisation and repair, as has been demonstrated previously. In contrast, raised intra-articular pressure lasting for only two hours resulted in a more complex picture: trabecular osteocytes were dead, whereas the bone-forming marrow was shown by fluorochrome labelling to remain viable, and to form appositional repair bone throughout the epiphysis. We concluded that transient vascular occlusion may cause the death of trabeculae despite intact perfusion of the bone. This type of change may be important in the pathogenesis of Perthes' disease

The anatomy of the autonomic sympathetic vasomotor nerve supply of bone was studied in rabbits by methods of histochemistry, and fluorescent and electron microscopy. Our observations show that the intraosseous vessels are richly supplied by adrenergic nerves. The large primary nerves are located on or about the surface of the vessel; the medium sized secondary nerves spiral around the long axis of vessels lying more deeply in the tunica adventitia; and the fine tertiary nerves form a rich plexus at the outer area of the tunica media. The tertiary nerves have various structures which probably contain neurotransmitter substance--that is, noradrenaline--and function as neuro-vasomuscular synapses. The sympathetic nerve supply of bone originates from the appropriate ganglion, and in the case of the tibial diaphysis it descends through the sciatic nerve and thereafter mainly through the medial popliteal nerve and enters the bone alongside the nutrient artery

This study shows that after intra-articular injection, aurothiomalate and colloidal gold of small (200 A) particle size were rapidly absorbed from joints while the larger, 300 A, particle size colloidal radioactive gold could not be found outside them. Larger particle size suspensions seem therefore more likely to remain localised in the joint and its lining synovium after intra-articular injection, the systemic absorption from the joint cavity diminishing with increasing particle size. It was also found that the intra-articular injection of small amounts of aurothiomalate, of colloidal gold and of colloidal radioactive gold produces identical degenerative lesions in the lining cells of the proximal convoluted tubules of the kidneys. These lesions were always found, although gold particles were demonstrated only in sampled kidney tissues of the animals injected with the soluble gold preparation whereas no gold could be detected in the tissues of animals injected with colloidal non-radioactive or radioactive gold. Electron microscopic evidence is presented to suggest the possibility that the mitochondria are the "target" organelles of the gold-induced cellular damage. Mitochondrial damage was demonstrated in liver and spleen in addition to the already described kidney damage. The correlation between structure and function of the mitochondrial changes is not clear, and ionic shifts may be both a cause and a result of damage.

Aims. Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting. Methods. Titanium-aluminium-vanadium (Ti6Al4V) screws were implanted in medial condyle of New Zealand giant rabbit knee. Study intervention consisted of induction heating of the screw head up to 70°C for 3.5 minutes after implantation using a portable device. Both knees were implanted, and induction heating was applied unilaterally keeping contralateral knee as paired control. Sterile screws were implanted in six rabbits, while the other six received screws coated with Staphylococcus aureus biofilm. Sacrifice and sample collection were performed 24, 48, or 96 hours postoperatively. Retrieved screws were sonicated, and adhered bacteria were estimated via drop-plate. Width of bone necrosis in retrieved femora was assessed through microscopic examination. Analysis was performed using non-parametric tests with significance fixed at p ≤ 0.05. Results. The width of necrosis margin in induction heating-treated knees ranged from 0 to 650 μm in the sterile-screw group, and 0 to 517 μm in the biofilm-infected group. No significant differences were found between paired knees. In rabbits implanted with sterile screws, no bacteria were detected. In rabbits implanted with infected screws, a significant bacterial load reduction with median 0.75 Log10 colony-forming units/ml was observed (p = 0.016). Conclusion. Induction heating was not associated with any demonstrable thermal bone necrosis in our rabbit knee model, and might reduce bacterial load in S. aureus biofilms on Ti6Al4V implants. Cite this article: Bone Joint Res 2024;13(12):695–702

Aims. Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release. Methods. A total of 24 rabbits underwent contracture-forming surgery with knee immobilization followed by remobilization surgery at eight weeks. At remobilization, one cohort underwent capsular release (n = 12), while the other cohort did not (n = 12). Both groups were divided into two subcohorts (n = 6 each) – one receiving IA injections of celecoxib, and the other receiving injections of vehicle solution (injections every day for two weeks after remobilization). Passive extension angle (PEA) was assessed in live rabbits at 10, 16, and 24 weeks, and disarticulated limbs were analyzed for capsular stiffness at 24 weeks. Results. IA celecoxib resulted in greater mean PEA at ten weeks (69.6° (SD 4.6) vs 45.2° (SD 9.6), p = 0.004), 16 weeks (109.8° (SD 24.2) vs 60.9° (SD10.9), p = 0.004), and 24 weeks (101.0° (SD 8.0) vs 66.3° (SD 5.8), p = 0.004). Capsular stiffness was significantly reduced with IA celecoxib (2.72 Newton per cm (N·cm)/° (SD 1.04), p = 0.008), capsular release (2.41 N·cm/° (SD 0.80), p = 0.008), and capsular release combined with IA celecoxib (3.56 N·cm/° (SD 0.99), p = 0.018) relative to IA vehicle (6.09 N·cm/° (SD 1.64)). Conclusion. IA injections of a celecoxib led to significant improvements in passive extension angles, with reduced capsular stiffness, when administered to rabbit knees with established experimental contracture. Celecoxib was superior to surgical release, and the combination of celecoxib and a surgical release did not provide any additional value. Cite this article: Bone Joint Res 2022;11(1):32–39

Aims. Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model. Methods. Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST). Results. Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups. Conclusion. The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases. Cite this article: Bone Joint Res 2024;13(3):127–135

Aims. This study aimed to demonstrate the promoting effect of elastic fixation on fracture, and further explore its mechanism at the gene and protein expression levels. Methods. A closed tibial fracture model was established using 12 male Japanese white rabbits, and divided into elastic and stiff fixation groups based on different fixation methods. Two weeks after the operation, a radiograph and pathological examination of callus tissue were used to evaluate fracture healing. Then, the differentially expressed proteins (DEPs) were examined in the callus using proteomics. Finally, in vitro cell experiments were conducted to investigate hub proteins involved in this process. Results. Mean callus volume was larger in the elastic fixation group (1,755 mm. 3. (standard error of the mean (SEM) 297)) than in the stiff fixation group (258 mm. 3. (SEM 65)). Pathological observation found that the expression levels of osterix (OSX), collagen, type I, alpha 1 (COL1α1), and alkaline phosphatase (ALP) in the callus of the elastic fixation group were higher than those of the stiff fixation group. The protein sequence of the callus revealed 199 DEPs, 124 of which were highly expressed in the elastic fixation group. In the in vitro study, it was observed that a stress of 200 g led to upregulation of thrombospondin 1 (THBS1) and osteoglycin (OGN) expression in bone marrow mesenchymal stem cells (BMSCs). Additionally, these genes were found to be upregulated during the osteogenic differentiation process of the BMSCs. Conclusion. Elastic fixation can promote fracture healing and osteoblast differentiation in callus, and the ability of elastic fixation to promote osteogenic differentiation of BMSCs may be achieved by upregulating genes such as THBS1 and OGN. Cite this article: Bone Joint Res 2024;13(10):559–572

Aims. The effects of remnant preservation on the anterior cruciate ligament (ACL) and its relationship with the tendon graft remain unclear. We hypothesized that the co-culture of remnant cells and bone marrow stromal cells (BMSCs) decreases apoptosis and enhances the activity of the hamstring tendons and tenocytes, thus aiding ACL reconstruction. Methods. The ACL remnant, bone marrow, and hamstring tendons were surgically harvested from rabbits. The apoptosis rate, cell proliferation, and expression of types I and III collagen, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), and tenogenic genes (scleraxis (SCX), tenascin C (TNC), and tenomodulin (TNMD)) of the hamstring tendons were compared between the co-culture medium (ACL remnant cells (ACLRCs) and BMSCs co-culture) and control medium (BMSCs-only culture). We also evaluated the apoptosis, cell proliferation, migration, and gene expression of hamstring tenocytes with exposure to co-culture and control media. Results. Compared to BMSCs-only culture medium, the co-culture medium showed substantially decreased early and late apoptosis rates, attenuation of intrinsic and extrinsic apoptotic pathways, and enhanced proliferation of the hamstring tendons and tenocytes. In addition, the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes in the hamstring tendons and tenocytes significantly increased in the co-culture medium compared to that in the control medium. Conclusion. In the presence of ACLRCs and BMSCs, the hamstring tendons and tenocytes significantly attenuated apoptosis and enhanced the expression of collagen synthesis, TGF-β, VEGF, and tenogenic genes. This in vitro study suggests that the ACLRCs mixed with BMSCs could aid regeneration of the hamstring tendon graft during ACL reconstruction. Cite this article: Bone Joint Res 2023;12(1):9–21

Aims. Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits. Methods. A group of 12 skeletally mature rabbits were randomly divided into two groups. One group received subcutaneous (SQ) saline, and a second group received SQ ketotifen injections. Biomechanical data were collected at eight, ten, 16, and 24 weeks. At the time of necropsy, posterior capsule tissue was collected for histopathological and gene expression analyses (messenger RNA (mRNA) and protein). Results. At the 24-week timepoint, there was a statistically significant increase in passive extension among rabbits treated with ketotifen compared to those treated with saline (p = 0.03). However, no difference in capsular stiffness was detected. Histopathological data failed to demonstrate a decrease in the density of fibrous tissue or a decrease in α-smooth muscle actin (α-SMA) staining with ketotifen treatment. In contrast, tryptase and α-SMA protein expression in the ketotifen group were decreased when compared to saline controls (p = 0.007 and p = 0.01, respectively). Furthermore, there was a significant decrease in α-SMA (ACTA2) gene expression in the ketotifen group compared to the control group (p < 0.001). Conclusion. Collectively, these data suggest that ketotifen mitigates the severity of contracture formation in a rabbit model of arthrofibrosis. Cite this article: Bone Joint Res 2020;9(6):302–310