Introduction. Metal on metal bearings are used especially in hip resurfacing. On the one hand, small bone preserving implants can be used. On the other hand recent studies found a variety of local and systemic side effects, for instance the appearance of pseudotumors, that are explained by pathologic biological reaction of the metal wear debris. The detailed mechanisms are still not understood until now. Thus it was the aim of this study to investigate the local reaction of metal wear particles and metal ions in a murine model. The hypothesis was that mainly metal ions provoke adverse histopathological reactions in vivo. Material and Methods. Three groups, each with 10 Balb / c mice were generated. Group A: injection of a 50 µl metal ion suspension at a concentration of 200 µg / l in the left knee. Group B: injection of a 50 µl 0,1 vol% metal particle suspension into the left knee joint. Group C (control group): injection of a 50 µl of 0,1 vol% PBS-suspension in the left knee. Incubation for 7 days, followed by euthanasia of the animals by intracardiac pentobarbital. The left and right knee, the lungs, kidneys, liver and spleen were removed. Histologic paraffin sections in 2 microns thickness were made, followed by HE (overview staining) and Movat (Pentachrom staining) staining. The histologic analysis was a done by a light microscopic evaluation of the subdivided visual fields at 200× magnification. Results. In the metal ions group compared with the control group an increasing thickness of synovial membrane as a sign of an inflammatory process was detected. Cartilage and subchondral bone as well as the adjacent bone marrow remain largely unchanged. In the metal particle group a thickenend synovial membrane was found and chondral, bone and periarticular tissue necrosis. In addition, pseudotumors with a complete destruction of the femoral or tibial bone were found. Conclusion. The initial hypothesis has to be rejected. it can be postulated that the metal ions have a certain inflammatory and destructive activity, but in the end it is the metal wear particles that lead to adverse tissue necrosis and to osteolytic destructions associated with a pseudotumor genesis

INTRODUCTION:. To avoid the early onset of osteoarthritis after partial meniscectomy an effective replacement of injured meniscal tissue would be desirable. The present study investigates the behaviour of a new silk derived scaffold supplied by Orthox Ltd. (Abingdon, UK) in an in vivo sheep model. METHODS:. The scaffolds where derived from silk fibres by processing into an open porous matrix. Nine sheep (4 ± 1 years) underwent partial meniscectomy at the anterior horn of the medial meniscus followed by implantation of a scaffold. The unoperated contralateral stifle joint served as control. After six months the animals were sacrificed and the joints inspected for inflammation. The Young's modulus of the tibial cartilage, meniscus and scaffold was determined by indentation or confined compression tests. All tissues were fixed in formaldehyde for histology. The data were analysed by a Wilcoxon and Mann-Whitney-U-test. RESULTS:. The sheep were free of lameness 4 days p.o. The macroscopic analysis of the genual region and of the synovial membrane showed no signs of inflammation. This was confirmed by histological sections of synovial membrane, meniscus and scaffold. In histology, amorphous material, some fibroblast-like cell clusters and connective tissue formation was visible inside the pores of the scaffold. There were no statistically significant differences between the Young's moduli of the three measuring points in the operated and unoperated stifle joints. The meniscal tissue showed a higher modulus than the scaffolds. The scaffold's modulus significantly increased after three months implantation. DISCUSSION & CONCLUSIONS:. The presented silk scaffold withstood the loads occurring during the six months implantation period. It showed promising properties concerning biocompatibility and cartilage protection and its mechanical properties started to approach those of meniscal tissue

INTRODUCTION:. One common surgical treatment of even early OA is the implantation of a Total Joint Arthroplasty. In case of younger patients this procedure is questionable. The present study investigates the behaviour of a new silk derived scaffold supplied by Orthox Ltd. (Abingdon, UK) in an in vivo sheep model. This scaffold allows replacing the damaged areas with a resurfacing technique and will avoid the implantation of a total joint in cases of early OA. METHODS:. The scaffolds where derived from silk fibres by processing into a composite of an open porous matrix in combination with a fibres mash with the same material and covered with a smooth surface. During the process the fluid silk can be casted in any shape. Eight sheep (4 ± 1 years) underwent a surgery where a large defect (2×1 cm) was created in the weight bearing zone of the medial condylus followed by implantation of a scaffold. The unoperated contra lateral stifle joint served as control. After six months the animals were sacrificed and the joints inspected for inflammation. The Young's modulus of the cartilage and scaffold was determined by indentation or confined compression tests. All tissues were fixed in formaldehyde for histology. The data were analysed by a Wilcoxon and Mann-Whitney-U-test. The roughness of the smooth surface was measured. Synovial fluid was harvested by punction before opening the joint and analysed for particle wear debris and for any signs of inflammation. RESULTS:. The sheep were free of lameness between the 2. nd. and latest the 4th days p.o. The macroscopic analysis of the genual region and the synovial membrane showed no signs of inflammation. The findings were confirmed by histological sections of synovial membrane and scaffold. In histology, amorphous material fibroblast-like cell clusters and connective bone tissue formation was visible inside the pores of the scaffold. The scaffols were complety integrated into the underlying bone. Synovial fluid showed no signs of inflammation only the IL6 level was slightly increased. No wear particles were found. No defetcs or mayor damage of the oponend cartilage were present. The measured roughness was between 13–18 nm. DISCUSSION & CONCLUSIONS:. The presented silk scaffold withstood the loads occurring during the six months implantation period. It showed very promising properties concerning biocompatibility and cartilage protection Its mechanical properties were simmilar of those of the surrounding cartilage. Since the material can be casted into any shape it offers a wide potential use in any large joint of the human body. The production of real patient specific implants will be easy to achieve

Previous study reported that intra-articular injection of MgSO4 could alleviate pain related behaviors in a collagenase induced OA model in rats. It provided us a good description on the potential of Mg2+ in OA treatment. However, the specific efficiency of Mg2+ on OA needs to be further explored and confirmed. The underlying mechanisms should be elucidated as well. Increasing attention has been paid on existence of synovial fluid MSCs (SF-MSCs) (not culture expanded) which may participate in endogenous reparative capabilities of the joint. On the other hand, previous studies demonstrated that Mg2+ not only promoted the expression of integrins but also enhanced the strength of fibronectin-integrin bonds that indicated the promotive effect of Mg2+ on cell adhesion, moreover, Mg2+ was proved could enhance chondrogenic differentiation of synovial membrane derived MSCs by modulating integrins. Based on these evidence, we hypothesize herein intra-articular injection of Mg2+ can attenuate cartilage degeneration in OA rat through modulating the biological behavior of SF-MSCs. Human and rat SF-MSCs were collected after obtaining Experimental Ethics approval. The biological behaviors of both human and rat SF-MSCs including multiple differentiation, adhesion, colony forming, proliferation, etc. were determined in vitro in presence or absence of Mg2+ (10 mmol/L). Male SD rats (body weight: 450–500 g) were used to establish anterior cruciate ligament transection and partial medial meniscectomy (ACLT+PMM) OA models. The rats received ACLT+PMM were randomly divided into saline (control) group and MgCl2 (0.5 mol/L) group (n=6 per group). Intra-articular injection was performed on week 4 post-operation, twice per week for two weeks. Knee samples were harvested on week 2, 4, 8, 12 and 16 after injection for histological analysis for assessing the progression of OA. On week 2 and 4 after injection, the rat SF-MSCs were also isolated before the rats were sacrificed for assessing the abilities of chondrogenic differentiation, colony forming and adhesion in vitro. Statistical analysis was done using Graphpad Prism 6.01. Unpaired t test was used to compare the difference between groups. Significant difference was determined at P < 0 .05. The adhesion and chondrogenic differentiation ability of both human and rat SF-MSCs were significantly enhanced by Mg2+ (10 mmol/L) supplementation in vitro. However, no significant effects of Mg2+ (10 mmol/L) on the osteogenic and adipogenic differentiation as well as the colony forming and proliferation. In the animal study, histological analysis by Saffranin O and Toluidine Blue indicated the cartilage degeneration was significantly alleviated by intra-articular injection of Mg2+, in addition, the expression of Col2 in cartilage was also increased in MgCl2 group with respect to control group indicated by immunohistochemistry. Moreover, the OARSI scoring was decreased in MgCl2 group as well. Histological analysis and RT-qPCR indicated that the chondrogenic differentiation of SF-MSCs isolated from Mg2+ treated rats were significantly enhanced compare to control group. In the current study, we have provided direct evidence supporting that Mg2+ attenuated the progression of OA. Except for the effect of Mg2+ on preventing cartilage degeneration had been demonstrated in this study, for the first time, we demonstrated the promoting effect of Mg2+ on adhesion and chondrogenic differentiation of endogenous SF-MSCs within knee joint that may favorite cartilage repair. We have confirmed that the anti-osteoarthritic effect of Mg2+ involves the multiple actions which refer to prevent cartilage degeneration plus enhance the adhesion and chondrogenic differentiation of SF-MSCs in knee joint to attenuate the progression of OA. These multiple actions of Mg2+ may be more advantage than traditional products. Besides, this simple, widely available and inexpensive administration of Mg2+ has the potential on reducing the massive heath economic burden of OA. However, the current data just provided a very basic concept, the exact functions and underlying mechanisms of Mg2+ on attenuating OA progression still need to be further explored both in vitro and in vivo. Formula of Mg2+ containing solution also need to be optimized, for example, a sustained and controlled release delivery system need to be developed for improving the long-term efficacy

There is currently no cure for osteoarthritis (OA), although there are ways to manage it, but most require quite invasive surgeries. There is a resident mesenchymal progenitor cell (MPC) population within the synovial membrane of the joint that have the ability to differentiate into bone, fat, and cartilage. We hypothesise that in vivo and in vitro cell surface marker expression comparisons of the MPCs can determine which population has the highest chondrogenic capacity and is best suited for future clinical trials. Method optimisation protocol: Synovial biopsies (2 or 5mm) were obtained from patients undergoing surgery. The biopsies were digested in either collagenase type I, IA, IV or II at a concentration of 0.5 or 1.0 mg/mL. Digestion was conducted at 37°C for 30, 60, 90 or 120min. To assay for the number of MPCs obtained, the cell suspension was stained with CD90 (a synovial MPC marker) and magnetically purified. The purified cells were then assayed by flow cytometry (Co-stained with a live/dead cell marker, BV510) or bright-field microscopy. Study protocol: Synovial tissues were digested in type IV collagenase for two hours to obtain a single cell suspension. The cells were subsequently stained with mesenchymal stem cell markers, including CD 90, CD 271, CD 44, CD73, and CD105, a macrophage marker, CD68. The macrophages were excluded and the remaining cells were index sorted into 96-well plates. The cells were expanded, and underwent 21-day chondrogenic, adipogenic, and osteogenic differentiation. Differentiation was assayed using RT-qPCR and histological methods. Additionally, the cells were re-analysed for marker expression after culturing. Optimisation: Synovial biopsies of 5mm produced a greater number of live CD90+ cells than 2mm biopsies. It was observed that type IV collagenase at 1mg/ML treatment for 120 min (hip) and 90 min (knee) obtained the greatest number of CD90+ MPCs from the synovium. Results: A single cell was isolated from an OA hip biopsy and was positive for the markers CD90, CD44, CD73, and negative for the markers CD68, CD271, CD105. Following differentiation, PCR analysis suggested that the cell line was able to differentiate into chondrocytes and adipocytes, but not osteoblasts. Histology data agreed with the PCR data with the adipocytes and chondrocytes having positive staining, whereas the osteoblasts were negative. FACS analysis following proliferation showed that the expression in vivo versus in vitro was the same except CD105 that became positive after proliferation in vitro. MPCs express cell surface markers that provide information as to populations have the best cartilage regeneration abilities. By determining the properties of the MPCs in OA hips that allow for better chondrogenic differentiation abilities in vitro, selecting the optimal cells for regenerating cartilage can be done more efficiently for novel cell therapies for OA

Alignment of total joint replacement in the valgus knee can be done readily with intramedullary alignment and hand-held instruments. Intramedullary alignment instruments usually are used for the femoral resection. The distal femoral surfaces are resected at a valgus angle of 5 degrees. A medialised entry point is advised because the distal femur curves toward valgus in the valgus knee, and the distal surface of the medial femoral condyle is used as reference for distal femoral resection. In the valgus knee, the anteroposterior axis is especially important as a reliable landmark for rotational alignment of the femoral surface cuts because the posterior femoral condyles are in valgus malalignment, and are unreliable for alignment. Rotational alignment of the distal femoral cutting guide is adjusted to resect the anterior and posterior surfaces perpendicular to the anteroposterior axis of the femur. In the valgus knee this almost always results in much greater resection from the medial than from the lateral condyle. Intramedullary alignment instruments are used to resect the proximal tibial surface perpendicular to its long axis. Like the femoral resection, resection of the proximal tibial surface is based on the height of the intact medial bone surface. After correction of the deformity, ligament adjustment is almost always necessary in the valgus knee. Stability is assessed first in flexion by holding the knee at 90 degrees and maximally internally rotating the extremity to stress the medial side of the knee, then maximally externally rotating the extremity to evaluate the lateral side of the knee. Medial opening greater than 4mm, and lateral opening greater than 5mm, is considered abnormally lax, and a very tight lateral side that does not open at all with varus stress is considered to be abnormally tight. Stability is assessed in full extension by applying varus and valgus stress to the knees. Medial opening greater than 2mm is considered to be abnormally lax, and a very tight lateral side that does not open at all with varus stress is considered to be too tight. Release of tight structures should be done in a conservative manner. In some cases, direct release from bone attachment is best (popliteus tendon); in others, release with pie-crusting technique is safe and effective. In knees that are too tight laterally in flexion, but not in extension, the LCL is released in continuity with the periosteum and synovial attachments to the bone. When this lateral tightness is associated with internal rotational contracture, the popliteus tendon attachment to the femur is also released. The iliotibial band and lateral posterior capsule should not be released in this situation because they provide lateral stability only in extension. The only structures that provide passive stability in flexion are the LCL and the popliteus tendon complex, so knees that are tight laterally in flexion and extension have popliteus tendon or LCL release (or both). Stability is tested after adjusting tibial thickness to restore ligament tightness on the lateral side of the knee. Additional releases are done only as necessary to achieve ligament balance. Any remaining lateral ligament tightness usually occurs in the extended position only, and is addressed by releasing the iliotibial band first, then the lateral posterior capsule, if needed. The iliotibial band is approached subcutaneously and released extrasynovially, leaving its proximal and distal ends attached to the synovial membrane. In knees initially too tight laterally in extension, but not in flexion, the LCL and popliteus tendon are left intact, and the iliotibial band is released. If this does not loosen the knee enough laterally, the lateral posterior capsule is released. The LCL and popliteus tendon rarely, if ever, are released in this type of knee. Finally, the tibial component thickness is adjusted to achieve proper balance between the medial and lateral sides of the knee. Anteroposterior stability and femoral rollback are assessed, and posterior cruciate substitution is done, if necessary, to achieve acceptable posterior stability

Introduction. Some patients complain ingrown pain or discomfort after implanting Co-Cr conventional endprosthesis of the hip. Some of this complaint may be attributable for effect on cartilage metabolism. It have been reported that ceramic is bioinert for biological tissue. On the other hand, metal including cobalt-chrome (Co-Cr) have some detrimental effect on biological tissue. However, there is no report concerning acetabular cartilage metabolism after hip endprosthesis implantation. In the present study, we hypothesized that ceramic head have small detrimental effect on cartilage cell metabolism. Specific aim of the study is to compare the protein level of inflammation related cytokines, amount of hyaluronic acid (HA) in culture media, and cartilage mRNA expression in organ culture model of hip end prosthesis implanted using ceramic head and Co-Cr head. Materials and Methods. Six acetabulum of 3 matured crossbred pig (average weight: 36 +/− 3.6kg) was retrieved. Animal experiment was performed under the rules of ethical committee of animal experiment. Average diameter of pig acetabulum was 26.3 +/− 0.6 mm. Just after sacrifice, mechanical loading using Instron testing machine with 26mm diameter of Co-Cr in right hip and Ceramic heads in left hip was performed in culture media. Ten thousand cycles of cyclic compression and rotation load (1.5kN to 0.15kN of compression and 12 degrees of rotation) to cartilage was applied at 1Hz (Figure 1). Culture media was analyzed for protein levels of inflammation related cytokines and amount of HA. Relative quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) from acetabular cartilage was performed as previously reported using specific primer sets for type II collagen, aggrecan, TNF-alpha, Interleukine-1 and 6, and MMP-1, 3, 13. Results. IL-1 beta protein level from culture media was significantly higher in Co-Cr than that in Ceramic (155+/−25.2 pg/ml vs. 86.3+/−9.6 pg/ml respectively). MMP-3 protein level had tendency to be higher in culture media from Co-Cr than that from Ceramic (16.3+/−10.6 ng/ml vs. 10.0+/−0.1 ng/ml respectively, p<0.05), however there was no significant difference. There were no significant differences of protein levels from culture media in MMP-1, IL-1a, and TNF between two groups. Amount of HA from culture media of Co-Cr group was significantly higher than that from Ceramic group (337+/−38.4 mg/ml versus 257+/−11.1 mg/ml respectively, p<0.05). Type II collagen mRNA expression was 3 times higher in Ceramic group than that in Co-Cr group. IL-1 beta mRNA expression was 4 times higher in Co-Cr group than that in Ceramic group. Other gene expression had no significant differences. Discussion. The present study showed that Co-Cr affects cartilage metabolism than Ceramic. Co-Cr group had higher protein level and mRNA expression of inflammation related cytokine, IL-1 beta, and higher HA. Concerning the mRNA expression from cartilage, type II collagen was significantly higher in Ceramic group. It has been reported that HA level is high in osteoarthritic joint. These report and our results showed that ceramic head have small detrimental effect on cartilage cell metabolism. There are limitations of the present study. Firstly, the sample size is small. Secondly, we did not evaluate synovial membrane metabolism

This study documents the gross and histologic structure of the infrapatellar plica, and fat pad, and adds to an earlier report to the COA. The important new findings are that the femoral attachment of the plica is an enthesis, and that the plica itself is. This study seeks to demonstrate that the structure of the fat pad (FP) and infrapatellar plica (IPP) is that of an enthesis organ. Twelve fresh frozen cadaver knees, each with an IPP, were dissected and the gross anatomic features recorded. The IPP and FP were harvested for study. Representative histologic sections were prepared on tissue fixed in 10% neutral buffered formalin, embedded in paraffin, cut at 4 microns on a rotatory microtome. Staining techniques included hematoxylin and eosin, Masson's trichrome, elastic stain and S100. Appropriate decalcification of sections of the femoral insertion of the IPP was performed. All sections were examined by light microscopy at low, medium and high power. IPP types included 8 separate, 1 split, 2 fenestrated, and one vertical septum. The origin of the IPP is a fibrous arc arising from the apex of the notch separate from the margin of the articular cartilage. This attachment site is the instant centreof rotation of the IPP and FP; they are thus not isometric. The central zone of the IPP consists of a mix of connective tissue types. Representative sections taken of the femoral attachment of the IPP display a transition zone between dense fibrillar collagen of the IPP, then fibrocartilage and cortical bone similar to a ligament attachment site or enthesis. The central plica histology is composed predominantly of dense regular connective tissue with variable clear space between the collagen bundles, and is thus ligamentous. There is abundant elastase staining throughout, as well as crimping of the collagen suggesting capacity for stretch. S100 staining demonstrates nerves around and in the substance of the IPP. The central body shows lobulated collections of mature adipose tissue admixed with loose connective tissue, containing abundant small peripheral nerves and vessels (all showing crimping and redundancy), merging with the dense fibrous tissue of the IPP. The FP is highly innervated, deformable, and fibro-fatty. Its histology shows lobules of fat, separated by connective tissue septa, which merge with the synovial areolar membrane surrounding the FP. The linked structures, IPP, central body, and FP occupy the anterior compartment, and function as an enthesis organ: the IPP tethers the FP via the central body and together they rotate around the femoral origin of the IPP. They are not isometric, and must stretch and relax with knee motion. The histology correlates with this requirement. The origin of the IPP is an enthesis, a new observation. Elastase staining, redundancy of vessels and nerves, crimping and redundancy of the dense connective tissue all reflect the requirement to deform. The fat pad merges with the central body, both highly innervated space fillers, tethered by the IPP, which is a non-isometric ligament, also containing nerves. The important clinical significance of these structures is that release of the IPP at the origin reuces or eliminates anterior knee pain in most

Bactericidal levels of antibiotics are difficult to achieve in infected total joint arthroplasty when intravenous antibiotics or antibiotic-loaded cement spacers are used, but intra-articular (IA) delivery of antibiotics has been effective in several studies. This paper describes a protocol for IA delivery of antibiotics in infected knee arthroplasty, and summarises the results of a pharmacokinetic study and two clinical follow-up studies of especially difficult groups: methicillin-resistant Staphylococcus aureus and failed two-stage revision. In the pharmacokinetic study, the mean synovial vancomycin peak level was 9242 (3956 to 32 150; sd 7608 μg/mL) among the 11 patients studied. Serum trough level ranged from 4.2 to 25.2 μg/mL (mean, 12.3 μg/mL; average of 9.6% of the joint trough value), which exceeded minimal inhibitory concentration. The success rate exceeded 95% in the two clinical groups. IA delivery of antibiotics is shown to be safe and effective, and is now the first option for treatment of infected total joint arthroplasty in our institution.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):31–6.