麻省理工大学：《Design of Medical Device》chapter 9 Effects of Implant on the Body: Biocompatibility.pdf_大学文库

9.2.1 Migration of Molecules(Soluble)and Particles(Insoluble); Lymphatic System Local and regional lymphadenopathy caused by wear particles released from joint replacement prostheses is becoming increasingly recognized as a possible complication of arthroplasty. Particles generated by mechanical wear of prostheses can leave the site of the implant via the lymphatics and become engulfed by macrophages within local and regional lymph nodes. Accumulation of cells containing particles causes enlargement of the lymph node and the characteristic histologic appearance of sinus histiocytosis. Distension and prominence of the lymphatic sinuses is due to the presence of large numbers of a) histiocytes derived from the cells that line the sinuses or b) macrophages derived from circulating monocytes. Multinucleated giant cells, resulting from the fusion of macrophages or histiocytes, might also be found in the dilated Sinuses nodes draining joints replaced with prostheses has been found in animal 3, 24 and huma ph Accumulation of polyethylene, polymethylmethacrylate, and metal particles in lymp studies2,3, 8, 12, a few of which have reported lymphadenopathy in operative patients, 15, 20.Total joint prostheses produce particulate debris through adhesive, abrasive, and fatigue( delamination) wear processes occurring 1)at the articulating interface between metal and polyethylene, 2) at the junctions of the modular portions of a modular total joint prosthesis, 3)at the interface between component and cement, or 4)at the interface between implant and bone. Polyethylene, polymethylmethacrylate, and metal particles are all capable of stimulating resorption of periprosthetic bone, 4. 9, 10), 16, 1 8, 19,21,25.,26. The adverse consequences of periprosthetic bone loss have focused a great deal of attention on the problems caused by wear particles locally at the implant-bone interface. Much less attention has been focused on the pathologic response to these particles at distant sites in the body The tissue response to wear particles is that of a foreign body reaction, with varying amounts of macrophages and foreign body giant cells, 24, 28. Synovial macrophages readily engulf particles released into the joint space. When the production of particulate debris exceeds the phagocytic capacity of synovial macrophages, excess particles a) migrate into periprosthetic tissue where they are ultimately phagocytosed by macrophages, that release agents that stimulate bone resorption, or b)enter lymphatic vessels. There is evidence that macrophages laden with partcles can also gain entry to the lymphatics. Macrophages present within lymph nodes endocytose free particles traveling within the lymphatic system. A steady influx of wear debris causes these macrophages to accumulate within the sinus of the lymph node. Over several years macrophages containing particles may become so abundant that they cause dilatation of nodal sinuses and node enlargement. The accumulation of histiocytes or macrophages within lymph node sinuses is described pathologically as sinus histiocytosis. The histopathologic response to polyethylene particles in lymph nodes and periprosthetic tissue is comparable. At both sites macrophages containing polyethylene have abundant, granular, eosinophilic cytoplasm, with small central nuclei. Polyethylene particles smaller than three micrometers are seen within individua cells, while larger particles are surrounded by foreign body giant cells

9.2.1 Migration of Molecules (Soluble) and Particles (Insoluble); Lymphatic System Local and regional lymphadenopathy caused by wear particles released from joint replacement prostheses is becoming increasingly recognized as a possible complication of arthroplasty. Particles generated by mechanical wear of prostheses can leave the site of the implant via the lymphatics and become engulfed by macrophages within local and regional lymph nodes. Accumulation of cells containing particles causes enlargement of the lymph node and the characteristic histologic appearance of sinus histiocytosis6. Distension and prominence of the lymphatic sinuses is due to the presence of large numbers of a) histiocytes derived from the cells that line the sinuses or b) macrophages derived from circulating monocytes. Multinucleated giant cells, resulting from the fusion of macrophages or histiocytes, might also be found in the dilated sinuses. Accumulation of polyethylene, polymethylmethacrylate, and metal particles in lymph nodes draining joints replaced with prostheses has been found in animal13,24 and human studies2,3,8,12, a few of which have reported lymphadenopathy in operative patients6,15,20. Total joint prostheses produce particulate debris through adhesive, abrasive, and fatigue (delamination) wear processes occurring 1) at the articulating interface between metal and polyethylene, 2) at the junctions of the modular portions of a modular total joint prosthesis, 3) at the interface between component and cement, or 4) at the interface between implant and bone . Polyethylene, polymethylmethacrylate, and metal particles are all capable of stimulating resorption of periprosthetic bone1,4,9,10,16,18,19,21,25,26 . The adverse consequences of periprosthetic bone loss have focused a great deal of attention on the problems caused by wear particles locally at the implant-bone interface. Much less attention has been focused on the pathologic response to these particles at distant sites in the body. The tissue response to wear particles is that of a foreign body reaction, with varying amounts of macrophages and foreign body giant cells8,24,28. Synovial macrophages readily engulf particles released into the joint space. When the production of particulate debris exceeds the phagocytic capacity of synovial macrophages, excess particles a) migrate into periprosthetic tissue where they are ultimately phagocytosed by macrophages, that release agents that stimulate bone resorption19, or b) enter lymphatic vessels25. There is evidence that macrophages laden with partcles can also gain entry to the lymphatics7. Macrophages present within lymph nodes endocytose free particles traveling within the lymphatic system. A steady influx of wear debris causes these macrophages to accumulate within the sinus of the lymph node3. Over several years macrophages containing particles may become so abundant that they cause dilatation of nodal sinuses and node enlargement. The accumulation of histiocytes or macrophages within lymph node sinuses is described pathologically as sinus histiocytosis. The histopathologic response to polyethylene particles in lymph nodes and periprosthetic tissue is comparable. At both sites, macrophages containing polyethylene have abundant, granular, eosinophilic cytoplasm, with small central nuclei. Polyethylene particles smaller than three micrometers are seen within individual cells, while larger particles are surrounded by foreign body giant cells22

Systemic Migration of Particles Derived from Implants There are numerous reports in the literature of migration of particles, released from implants, to lymph nodes and many organs. The spread particles of silicone elastomer and liquid droplets(namely, from breast implants) is well documented(see for review Travis, et al."). The translocation of these particles has been found to be due to a) migration through soft tissues, b) entry into the lymphatic system, and c) direct entry into the vascular system". Silicone particles have been found to migrate from breast implants through soft tissue to sites as distant as the groin. The finding of silicone lymphadenopathy in axillary lymph nodes is common in patients with breast implants. The hematogenous dissemination of silicone to viscera has also been reported as a result of soft tissue injection of the material22. In the orthopedic literature, silicone lymphadenopathy has become a common finding in patients receiving finger joint prostheses made of silicone elastomer 6, 7 Reports documenting dissemination of particles in the lymphatic system from total joint prostheses are mounting, suggesting that this phenomenon may be more common than previously thought Table 1). There are several animal studies documenting lymphatic spread of polyethylene particles to regional nodes3, 24. bos et al. recently provided evidence from human autopsies that polyethylene, polymethylmethacrylate, and metal particles released from stable total hip replacements spread to inguinal, parailiac, and paraaortic lymph nodes as early as 1.5 years following implantationof the prosthesis. Sinus histiocytosis in association with wear particles of polyethylene has been an incidental finding in lymph nodes biopsied at revision arthroplasty 4, and the staging of prostate,0 and breast cancer. Adenopathy related to an implant is not limited to total hip and knee replacement prostheses. O Connell recently reported a case of axillary histiocytic lymphadenopathy in association with polyethylene wear particles from a total shoulder Kinetics of Particle migration from joints and bone The kinetics of migration of particles from joints and osseous sites have been the subject of several investigations. Noble, et al., investigated the leakage of particles labeled with a albumin, carbonized microspheres, gold colloid, and ferric hydroxide, with sizes ranging from m radioisotope from intra-articular injection sites in the rabbit knee; particles included human ser hirty nanometers to tens of micrometers. Approximately l per cent of the injected dose of ferric hydroxide("inert")particles, less than one micrometer in diameter, migrated from the joint twenty four hours after injection. The kinetics of migration(leakage rate)of particles from the joint space was related to particle size; there was an order-of-magnitude difference in the leakage rates (2.2 to 0.1 per cent after twenty four hours) for particles ranging from less than 0. 1 to 15.0 In other studies a canine model was used to investigate the spread of cell-sized radioactive microspheres from the distal femur into the lymphatic system, venous drainage, and local tissue. In this model microspheres, fifteen micrometers in diameter, were injected into the medullary canal of the femur. Particles entered directly into the venous system( within fifteen seconds of

Systemic Migration of Particles Derived from Implants There are numerous reports in the literature of migration of particles, released from implants, to lymph nodes and many organs. The spread particles of silicone elastomer and liquid droplets (namely, from breast implants) is well documented (see for review Travis, et al.25). The translocation of these particles has been found to be due to a) migration through soft tissues, b) entry into the lymphatic system, and c) direct entry into the vascular system22. Silicone particles have been found to migrate from breast implants through soft tissue to sites as distant as the groin5. The finding of silicone lymphadenopathy in axillary lymph nodes is common in patients with breast implants23. The hematogenous dissemination of silicone to viscera has also been reported as a result of soft tissue injection of the material22. In the orthopedic literature, silicone lymphadenopathy has become a common finding in patients receiving finger joint prostheses made of silicone elastomer6,7. Reports documenting dissemination of particles in the lymphatic system from total joint prostheses are mounting, suggesting that this phenomenon may be more common than previously thought (Table 1). There are several animal studies documenting lymphatic spread of polyethylene particles to regional nodes13,24. Bos et al. recently provided evidence from human autopsies that polyethylene, polymethylmethacrylate, and metal particles released from stable total hip replacements spread to inguinal, parailiac, and paraaortic lymph nodes as early as 1.5 years following implantationof the prosthesis3. Sinus histiocytosis in association with wear particles of polyethylene has been an incidental finding in lymph nodes biopsied at revision arthroplasty14, and the staging of prostate2,6 and breast cancer15. Adenopathy related to an implant is not limited to total hip and knee replacement prostheses. O’Connell recently reported a case of axillary histiocytic lymphadenopathy in association with polyethylene wear particles from a total shoulder replacement15. Kinetics of Particle Migration from Joints and Bone The kinetics of migration of particles from joints and osseous sites have been the subject of several investigations. Noble, et al., 14 investigated the leakage of particles labeled with a radioisotope from intra-articular injection sites in the rabbit knee; particles included human serum albumin, carbonized microspheres, gold colloid, and ferric hydroxide, with sizes ranging from thirty nanometers to tens of micrometers. Approximately 1 per cent of the injected dose of ferric hydroxide ("inert") particles, less than one micrometer in diameter, migrated from the joint twenty four hours after injection. The kinetics of migration (leakage rate) of particles from the joint space was related to particle size; there was an order-of-magnitude difference in the leakage rates (2.2 to 0.1 per cent after twenty four hours) for particles ranging from less than 0.1 to 15.0 millimeters. In other studies a canine model was used to investigate the spread of cell-sized radioactive microspheres from the distal femur into the lymphatic system, venous drainage, and local tissue17. In this model microspheres, fifteen micrometers in diameter, were injected into the medullary canal of the femur. Particles entered directly into the venous system (within fifteen seconds of

injection) and were effectively filtered by the lungs, thus preventing dissemination in the arterial system. No migration of particles from the femur into the lymphatic system was found after four days. However, similar microspheres injected into soft tissue in the distal femur were found in the iliac lymph nodes in two of nine animals after this time period. In neither of these animals were particles found in the lungs. A subsequent study demonstrated that particles as large as 100 micrometers, injected into the canal of the distal femur, migrated to the lungs within fifteen minutes of injection. These results suggest that under certain conditions particles generated by wear might directly enter the venous system. The majority of these particles would be filtered in the lung, preventing hematogenous spread. Collectively the investigations indicate that a marked number of particles can be disseminated to various sites in the body within hours after their generation. Clinical Implications Lymphadenopathy secondary to the accumulation of wear particles in sinus macrophages may cause confusion regarding the appropriate diagnosis, especially in cases where malignancy is suspected. Shinto, et al., recently reported a case of a nineteen year-old man who presented with right inguinal pain and a three x three centimeter palpable mass, three years after placement of a right total knee replacement following resection of an osteosarcoma. The lymph node was biopsied to evaluate for suspected metastatic recurrence of osteosarcoma. Histologic examination revealed sinus histiocytosis due to metal particles released from the knee prosthesis. There was no evidence of malignancy The ultimate fate of particles released from total joint prostheses is unknown. A recer report suggests that metallic particles from orthopedic prostheses may pass through the lymphatics and gain a systemic distribution. The clinical sequelae of polyethy lene particles in lymph nodes and other organs is unknown. However, the fact that disseminated polyethylene particles cannot be removed focuses attention on investigations of the long term host response to polyethylene particles

injection) and were effectively filtered by the lungs, thus preventing dissemination in the arterial system. No migration of particles from the femur into the lymphatic system was found after four days. However, similar microspheres injected into soft tissue in the distal femur were found in the iliac lymph nodes in two of nine animals after this time period. In neither of these animals were particles found in the lungs. A subsequent study11 demonstrated that particles as large as 100 micrometers, injected into the canal of the distal femur, migrated to the lungs within fifteen minutes of injection. These results suggest that under certain conditions particles generated by wear might directly enter the venous system. The majority of these particles would be filtered in the lung, preventing hematogenous spread. Collectively the investigations indicate that a marked number of particles can be disseminated to various sites in the body within hours after their generation. Clinical Implications Lymphadenopathy secondary to the accumulation of wear particles in sinus macrophages may cause confusion regarding the appropriate diagnosis, especially in cases where malignancy is suspected. Shinto, et al., recently reported a case of a nineteen year-old man who presented with right inguinal pain and a three x three centimeter palpable mass, three years after placement of a right total knee replacement following resection of an osteosarcoma20. The lymph node was biopsied to evaluate for suspected metastatic recurrence of osteosarcoma. Histologic examination revealed sinus histiocytosis due to metal particles released from the knee prosthesis. There was no evidence of malignancy. The ultimate fate of particles released from total joint prostheses is unknown. A recent report suggests that metallic particles from orthopedic prostheses may pass through the lymphatics and gain a systemic distribution12. The clinical sequelae of polyethylene particles in lymph nodes and other organs is unknown. However, the fact that disseminated polyethylene particles cannot be removed focuses attention on investigations of the long term host response to polyethylene particles