Multinuclear Foreign Body Giant Cells Research Articles

Biocompatibility and osteoconduction of macroporous silk fibroin implants in cortical defects in sheep

The goal of the presented study was to compare the biocompatibility and cellular responses to porous silk fibroin (SF) scaffolds produced in a water-based (UPW) or a solvent based process (HFIP) using two different SF sources. For that reason, four different SF scaffolds were implanted (n=6) into drill hole defects in the cancellous bone of the sheep tibia and humerus. The scaffolds were evaluated histologically for biocompatibility, cell–material interaction, and cellular ingrowth. New bone formation was observed macroscopically and histologically at 8weeks after implantation. For semiquantitative evaluation, the investigated parameters were scored and statistically analyzed (factorial ANOVA). All implants showed good biocompatibility as evident by low infiltration of inflammatory cells and the absent encapsulation of the scaffolds in connective tissue. Multinuclear foreign body giant cells (MFGCs) and macrophages were present in all parts of the scaffold at the material surface and actively degrading the SF material. Cell ingrowth and vascularization were uniform across the scaffold. However, in HFIP scaffolds, local regions of void pores were present throughout the scaffold, probably due to the low pore interconnectivity in this scaffold type in contrast to UPW scaffolds. The amount of newly formed bone was very low in both scaffold types but was more abundant in the periphery than in the center of the scaffolds and for HFIP scaffolds mainly restricted to single pores.

RANKL in the osteolysis of AES total ankle replacement implants

Peri-implant tissue reactions in failed total ankle replacement (TAR) are characterized by early developing peri-implant osteolysis. The hypothesis of the study was that this reaction is mediated by receptor activator of nuclear factor kappa B ligand (RANKL).Samples of peri-prosthetic tissues from failed TAR implants were stained for macrophages, RANKL, its receptor RANK and osteoprotegerin (OPG), and compared to control samples.The failed TAR implants were surrounded by implant capsule, synovial lining-like interface membrane or necrotic tissues. Infiltrating scavenger receptor I positive CD163+ macrophages were frequent, in particular around necrotic soft tissues or bone sequestrate, and possibly in part formed due to ischemia and mechanical factors. In contrast, implant-derived wear debris was scanty. Still many RANK+ macrophages were often seen in close contact with RANKL+ mesenchymal cells, whereas OPG was mostly located at a distance in vascular endothelial cells. Foreign body giant cells were frequent.RANKL seems to stimulate locally accumulated CD163+ RANK-expressing cells to fusion, which leads to the local formation of multinuclear foreign body giant cells (and probably of osteoclasts). Therefore, peri-implant osteolysis in early TAR implant failure seems to be caused by the RANKL-driven chronic foreign body inflammation directed against, not implant-derived particles, but against necrotic autologous tissues.

Histomorphology of thrombus organization, neointima formation, and foreign body response in retrieved human aneurysms treated with hydrocoil devices

Biological processes, such as thrombus organization, endothelialization, and foreign body response, that occur following embolization of intracranial aneurysms are poorly understood. We examined 13 human aneurysms (retrieved at autopsy 1-74 days postembolization) treated with hybrid hydrogel-platinum coil devices and platinum coils. The specimens were embedded in methyl methacrylate and ground sections were surface stained. Using light microscopy, thrombus organization in the sac, endothelialization of the neck, and foreign body response to the embolic devices were determined. The area percentages of the sac occupied by embolic devices and unorganized thrombus were quantified using image analysis. Thrombus organization increased over time, but was incomplete up to 74 days post-treatment. Neointima formation had started at 5 days upon dense fibrin depositions and progressed to form a new vessel wall at 74 days. The foreign body response to the hydrogel was characterized by mononuclear macrophages, while platinum coils were surrounded by multinuclear foreign body giant cells. Histometric aneurysm occlusion ranged from 89 to 100% and embolic devices occupied 31-64% of the aneurysm sac. These findings showed that the hydrogel-based devices occupied a large percentage of the aneurysm sac, provided a framework for thrombus organization to occur, and elicited less severe foreign body response than platinum coils.

Tissue reaction to intramuscular injection of resorbable polymer microparticles

Tissue reaction to implantation of polymeric microparticles from resorbable polymer (polyhydroxybutyrate) is characterized by slight inflammatory reaction and pronounced progressive macrophage infiltration with the presence of mono- and multinuclear foreign body giant cells resorbing the polymeric matrix. No fibrous capsules were formed around the polymeric microparticles; neither necrosis nor other adverse morphological changes and tissue transformation in response to implantation of the PHB microparticles were recorded. The results indicate good prospects of using polyhydroxybutyrate for the construction of long-acting dosage forms as microparticles for intramuscular injection.

Biocompatibility and functionality of the degradable polymer alkylene bis(dilactoyl)‐methacrylate for screw augmentation in vivo

Recently, a new degradable polymer has been developed on the basis of alkylene bis(dilactoyl)-methacrylate as an alternative material for screw augmentation. The polymer has been investigated in vitro and in a short-term experiment in rabbits exhibiting promising results. The aim of the present study was to investigate its long-term biocompatibility and mechanical functionality in a large animal model. The polymer was used for screw augmentation in the cancellous bone of the femoral condyle and tibia epiphysis of 12 sheep and was compared to polymethylmethacrylate (PMMA) augmented and nonaugmented screws. After an implantation period of 6 months, bone, regional lymph nodes, and several organs were histologically evaluated. The mechanical efficacy was investigated by a biomechanical pullout test. A lot of mononuclear macrophages and multinuclear foreign body giant cells with incorporated polymer particles indicate strong inflammatory reactions. Large osteolysis zones with osteoclasts were found in the surrounding polymer. The polymer was fragmented but not substantially degraded. Polymer particles were also found in the regional lymph nodes. Lung, liver, kidney, and spleen did not show any pathological signs. The pullout force of screws augmented with the new polymer was significantly reduced in comparison to PMMA augmented and nonaugmented screws, respectively. It was concluded that the material has poor biocompatibility and cannot be recommended for clinical application as screw augmentation material.

Fusion disability of embryonic osteoclast precursor cells and macrophages in the microphthalmic osteopetrotic mouse

Osteoclast formation in the microphthalmic osteopetrotic (mi) mouse was studied from very early embryonic to newborn stages. Embryonic and fetal mi/mi osteoclasts, generated during the period before bone marrow is formed in the long bones, were predominantly mononuclear and lacked ruffled borders. These cells did, however, show many osteoclastic morphologic and functional properties, such as an abundance of mitochondria, positive succinic dehydrogenase and acid phosphatase reactions, and close contact with and resorption of the calcified cartilage matrix (though diminished). These osteoclastic mononuclear cells appeared in vivo as well as in organ cultures of fetal metatarsal bones with their intact periostea. They also were observed in co-cultures of periosteum-free fetal metatarsal bones, with several extraneous sources of osteoclast precursors: yolk sacs and abdominal regions of 9- and 11-day-old embryos, fetal livers, and precultured mononuclear phagocytes isolated from the fetal liver. In contrast, +/+ osteoclasts were always multinuclear, functioned normally in resorbing the calcified cartilage matrix, and had ruffled borders in vivo as well as when derived from the above-mentioned sources. Fetal liver-derived mi/mi macrophages also failed to form multinuclear foreign body giant cells as opposed to +/+ macrophages in granulomas on implanted pieces of Melinex. The fusion failure of cells derived from embryonic and fetal extramedullary mi/mi monocyte/macrophage sources contrasted with the occurrence of multinuclear osteoclasts and foreign body giant cells derived from precursors from the bone marrow in young mi/mi mice. We conclude that the fusion defect of mi/mi osteoclast precursor cells is already present in their ancestry in blood cell-forming organs of very young embryos and that these cells differentiate into mononuclear osteoclasts that function inefficiently in prenatal bone. We presume that in fully developed bone marrow, local factors are favorable for abolishing the fusion defect.

Silicone synovitis of the wrist

Foreign body giant cell synovitis and focal bony destruction requiring secondary surgery developed in nine patients after carpal and radiocarpal arthroplasty with silicone rubber implants. Synovitis followed silicone rubber replacement of the lunate in four patients, the carpal scaphoid in two patients, and the trapezium in one patient, trapezial resurfacing hemiarthroplasty in one patient, and total wrist arthroplasty in one patient. All the removed implants were deformed. Some had changed in color from clear white at the time of insertion to yellow-white or deep yellow upon removal. Scanning electron microscopy of a silicone rubber implant of the lunate removed from one patient revealed extensive fibrillation in the capitate fossa. Light microscopy of the synovium revealed hyperplasia and hundreds of fragments of silicone particulate debris throughout the tissue adjacent to the implant. The silicone debris was surrounded by multinuclear foreign body giant cells in the eight patients from whom the synovium was studied. All patients required revision surgery. We believe that in the patients studied, synovitis represented a biologic reaction to the silicone fragments found scattered throughout the synovium for the following reasons: The synovitis found was not present before surgery (except in the patient with rheumatoid arthritis); the synovitis found was not associated with the condition for which replacement arthroplasty was performed (except in the patient with rheumatoid arthritis); synovitis subsided after implants were removed; and synovitis was noted histologically in areas of silicone debris and appeared directly related to silicone seeding. Fibrillation, fragmentation, and local seeding of silicone after carpal or radiocarpal arthroplasty appear related to gradual deformation of the implant, which was the result of repeated compressive loading and shearing. Clinically significant complications of rubber carpal or radiocarpal arthroplasty with silicone rubber implants may develop from silicone synovitis.

Ultrastructure of multinuclear giant cells of a human vocal cord Teflon granuloma.

The ultrastructural characteristics of multinuclear foreign-body giant cells (MCG) in a human vocal cord Teflon granuloma are described. The cells were found to contain varying numbers of Teflon particles within their cytoplasm. The particles, rounded or oval in shape, were surrounded by a rather electron-dense membrane. Numerous lysosomal structures were discerned within the cells. The fine structure of MCG in granulomas induced by foreign materials other than Teflon has already been described in man as well as in several experimental animals, and the Teflon MCG resembled these cells in many respects. No evidence of malignant change was found.