Comparison of replacement prostheses for segmental defects of bone. Different porous coatings for extracortical fixation

The extent of extracortical bone-bridging and ingrowth into porous-coated prostheses for the stabilization of segmental defects was studied in a canine model. Initial fixation of the implant was achieved using bone cement. Autogenous bone grafts were applied over the porous-coated segmental portion of the prosthesis to stimulate the ingrowth and formation of bone. At twelve weeks, bone-bridging and ingrowth occurred uniformly in both the titanium fibermesh and the cobalt-chromium-molybdenum beaded prostheses. Maximum formation of osseous tissue over the implants occurred at two to four weeks. More bone formed in the posterior aspect of the prosthesis. At twelve weeks, 26 per cent of the porous space of the titanium fibermesh prosthesis and 47 per cent of the porous space of the cobalt-chromium-molybdenum beaded prosthesis were filled with bone. The torsional strength and stiffness of the prosthetic midsection that contained a conical coupling joint were increased significantly due to bone-bridging and ingrowth. The cortical bone that was apposed to the segmental prosthesis showed an increase in porosity. The use of bone cement did not appear to impede new-bone formation extracortically. The initial stability of the implant and the application of sufficient autogenous bone grafts are two important factors that contribute to the ultimate stable fixation of an implant by extracortical bone formation.     

Short periods of oscillating fluid pressure directed at a titanium-bone interface in rabbits lead to bone lysis

Fluctuating high fluid pressures have been reported in pseudojoints after total hip arthroplasty, and may be present throughout the effective joint space. When the pressure extends locally to the bone implant interface, we hypothesized that it might have led to bone resorption. We developed an experimental implant model to study whether oscillating fluid pressure, applied during 2 hours a day, can lead to osteolysis at the bone implant interface. 12 mature rabbits received a titanium implant, which was allowed to osseointegrate. Thereafter, fluid pressure was applied to a specific area of the titanium bone interface at the periosteal side of the cortex in 6 of the rabbits. the pressure, applied during 2 hours a day for 14 days, oscillated between 70 and 150 mm Hg, with a frequency of 0.1 Hz. Bone resorption was not found in any of the control animals, but it occurred under 4 implants exposed to fluid pressure (p = 0.03; Fisher's exact test). Localized osteolytic lesions had developed, with evidence of osteocyte death in the surrounding cortical bone. in 1 of the 2 specimens without osteolysis, there was evidence of fluid leakage into the soft tissues. in 4 specimens (3 with and 1 without osteolysis), bone formation was observed at the endosteal side opposite to the pressure zone. This did not occur in the controls. No signs of infection were observed.

Our findings indicate that oscillating fluid pressure, even when present only during short periods, can lead to osteolysis and may be a cause of prosthetic loosening. Endosteal bone apposition may be a result of the interstitial flow that was created, giving false signals of mechanical load to the osteo-cytes.     

Effect of submicron polyethylene particles on an osseointegrated implant: an experimental study with a rabbit patello-femoral prosthesis

In a rabbit model of a weight bearing, articulating prosthetic joint we repeatedly injected submicron particles of Ultra-High-Molecular-Weight-Polyethylene (UHMWPE) produced in a hip simulator. The contralateral knee with the same prosthesis was injected with carrier (NaCl) without UHMWPE. Histomorphometrical studies on undecalcified cut and ground sections at 26 and 42 weeks involved quantifications of the entire bone to metal contact and the bone area around each implant. We found no statistically significant differences between test and control groups, and the UHMWPE debris did not induce any significant osteolysis, indicating that an osseointegrated implant with a sealed interface may not be affected by UHMWPE debris or progress to aseptic loosening.     

The significance of wear and material fatigue in loosening of hip prostheses

Particles created by wear and disintegration of implant materials give rise to foreign body reactions in the tissue surrounding joint endoprostheses. Histiocytes and foreign body giant cells phagocytize the particles released and form granulomas, which lead in turn to remodelling and resorption of the bone at the interface between implant and bone. As a consequence of this, osteolysis develops, which may lead to loosening and complete failure of fixation of the implant. Radiographically, the areas of osteolysis appear as localized, round, oval or oblong scalloping defects or as radiolucent lines in the endosteal sections of the bone immediately adjacent to the implants. This paper reports on 21 hip joint endoprostheses in which polyethylene and bone cement particles induced large areas of osteolysis at the bone/cement interface. In 8 cases the polyethylene particles originated from the convex joint surfaces of ball heads in "soft-top" endoprostheses (with or without simultaneous replacement of the acetabulum by a metal cup), and in 5 cases they originated from the anchoring surfaces of non-cemented cone-shaped screw-in sockets (Endler type); osteolysis and loosening of these endoprostheses appeared on average 48.2 and 76.6 months after implantation, respectively. The bone cement fragments came from the bone cement mantle of the femur, which had become fractured, disrupted and crushed, in 8 cases of total hip replacement with cemented prostheses; osteolysis appeared on average 87 months after primary implantation in these cases. Tissue samples taken at revision surgery from the joint capsule, the bone/cement interface and the osteolytic areas were processed into histological sections for microscopy and examined in the usual way. The type and amount of phagocytized material were subjected to semiquantitative analysis. We were able to show that osteolysis at the bone/cement interface can be induced by foreign body reactions to abraded polyethylene particles alone as well as by reactions to fragmented bone cement. The morphology of the tissue reaction to particles of the different materials is quite similar. The effect of the foreign body granulomas depends less on the type of the polymer than on the amount of abrasion and fragmentation products released into the surrounding tissue. This again proves that the life-time of joint endoprostheses depends essentially on factors influencing the wear rate. Polymer materials, with low wear resistance, are unsuitable for convex joint surfaces and for direct fixation to bone.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cellular reactions in hip prosthesis loosening.

Based on the results obtained in histological examinations carried out on periprosthetic tissues in a large series of cases of prosthetic hip joint explants, the authors analyze the cellular events that may occur in loosening phenomena as compared to what occurs in the paraphysiological repair process that is observed in the stable prosthesis. Like other authors, they believe that the principal role in the mechanism of loosening is played by macrophages which are recalled in a large number, at times together with multinucleate giant cells, at the bone-implant interface, after micromovements of the prosthesis and the formation of wear particles have occurred. The macrophages would be capable of favoring resorption of the periprosthetic bone tissue, producing areas of osteolysis in which the transmission of the mechanical stress of loading is modified. The ensuing prosthetic instability increases wear phenomena, causes a greater amount of osteolysis, and, in a vicious cycle, loss of the relationship between bone and implant, and, thus, prosthetic loosening. Finally, the authors report a hypothesis on the pathogenesis of the phenomenon, based on which non-physiological stress, associated with wear and eventually infection, leads to loosening.     

The effects of local and systemic alendronate delivery on wear debris‐induced osteolysis in vivo

We investigated the effects of locally and systemically administered alendronate on wear debris‐induced osteolysis in vivo. Endotoxin‐free titanium particles were injected into rabbit femurs, prior to insertion of a nonweight‐bearing polymethylmethacrylate plug into the distal femur canal. Then the particles were repeatedly injected into the knee 2, 4, and 6 weeks after the implantation. Alendronate was incorporated at three different concentrations (0.1, 0.5, and 1.0 wt %) into bone cement for local delivery. For systemic delivery, alendronate was subcutaneously injected (1.0 mg/kg/week) 1 week after the implantation and then once a week until sacrifice. Eight weeks postoperatively, there was significant evidence of osteolysis surrounding the plug in the control group compared with markedly blocked osteolysis in the 0.5 wt % and the 1.0 wt % groups, and the systemic group. There was a concentration‐dependent effect of alendronate‐loaded bone cement on the improvement of peri‐prosthetic bone stock. Notably, no significant differences were found between the 0.5 wt % and the systemic group in peri‐prosthetic bone stock and implant fixation. Collectively, although the biological efficacy after the systemic delivery of alendronate was slightly higher than that in the local treatment groups, alendronate‐loaded bone cement may be therapeutically effective in inhibiting titanium particle‐induced osteolysis in vivo. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:893–899, 2010     

Bone particles disturb new bone formation on the interface of the titanium implant after reaming of the marrow cavity

Histomorphometric studies were conducted in rats to determine whether bone particles would disturb new bone formation on the interface of titanium implants inserted after reaming of the marrow cavity. In eighty 10-week-old female Wistar rats, smooth-surfaced titanium alloy implants were inserted bilaterally into the marrow cavity after reaming in the distal femur. There were three experimental groups: in the irrigated femora, sterile saline was flushed through the medullary canal; in the particle femora, autologous bone particles were inserted into the intramedullary cavity; and in the reamed femora, the implant was inserted without procedures after reaming. The rats were sacrificed at one, two, four or eight weeks postoperatively, and Villanueva bone staining was applied for histomorphometric studies. The bone volume of new bone on the interface of the implant in the irrigated femora was greater than that in the particle or the reamed femora throughout the study period. The results suggest that clearance of bone particles by irrigation after reaming of the marrow cavity significantly facilitates new bone formation on the interface of implants by one week. The findings also suggest the potential clinical application of total canal irrigation prior to insertion of cementless femoral components as well as cemented prosthesis.     

人工全髋聚乙烯假体磨损及其生物学效应

目的 探讨人工关节聚乙烯磨损与假体松动的关系。方法 采用光镜与电镜对15例人工髋关节翻修病例的聚乙烯假体臼杯内表面及假体周围软组织作形态学观察。进而在动物实验中观察微小聚乙烯磨损颗粒促使骨吸收性细胞因子增加，植入物周围骨溶解以及植入物-骨整合强度下降的生物效应。结果 聚乙烯假体在人工关节松动形成时均明显磨损，聚乙烯磨损颗粒诱发机体单核-巨噬细胞增殖并分泌骨吸收性细胞因子。结论 聚乙烯磨损与假体松动密度相关。其中生物因素是引起假体松动的主要途径。     

Effect of submicron polyethylene particles on an osseointegrated implant

In a rabbit model of a weight bearing, articulating prosthetic joint we repeatedly injected submicron particles of Ultra-High-Molecular-Weight-Polyethylene (UHMWPE) produced in a hip simulator. The contralateral knee with the same prosthesis was injected with carrier (NaCl) without UHMWPE. Histomorphometrical studies on undecalcified cut and ground sections at 26 and 42 weeks involved quantifications of the entire bone to metal contact and the bone area around each implant. We found no statistically significant differences between test and control groups, and the UHMWPE debris did not induce any significant osteolysis, indicating that an osseointegrated implant with a sealed interface may not be affected by UHMWPE debris or progress to aseptic loosening.     

Low dose metal particles can induce monocyte/macrophage survival

Aseptic loosening results in pain, loss of function, and ultimately prosthetic joint failure and revision surgery. The generation of wear particles from the prosthesis is a major factor in local osteolysis. We investigated the effects of such wear particles on the survival of monocytes and macrophages, populations implicated in wear particle‐driven pathology. Particles from titanium aluminum vanadium (TiAlV) and cobalt chromium (CoCr) alloys were generated in‐house and were equivalent in size (0.5–3 µm) to those seen in patients. Human CD14⁺ monocytes and murine bone marrow‐derived macrophages (BMM) were treated with TiAlV and CoCr particles in vitro, and cell survival was assayed. Both particles increased monocyte and macrophage survival in a dose‐dependent manner, with an optimal concentration of around 10⁷ particles/mL. Conditioned media from particle‐treated BMM also increased macrophage survival. Studies with antibody blockade and gene‐deficient mice suggest that particle‐induced BMM survival is independent of endogenous CSF‐1 (M‐CSF), GM‐CSF, and TNFα. These data indicate that wear particles can promote monocyte/macrophage survival in vitro possibly via an endogenous mediator. If this phenomenon occurs in vivo, it could mean that increased numbers of macrophages (and osteoclasts) would be found at a site of joint implant failure, which could contribute to the local inflammatory reaction and osteolysis. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1481–1486, 2009     

Bone graft incorporation around titanium-alloy- and hydroxyapatite-coated implants in dogs.

To evaluate cancellous allogenic bone graft incorporation into porous-coated implants, the fixation of titanium alloy-(Ti) and hydroxyapatite-(HA) coated implants with and without bone graft was compared. An unloaded model with unilateral carragheenin-induced osteopenia of the knee was used in 12 mature dogs. Ti- and HA-coated cylinders were implanted in the distal femoral condyles and centralized in 2-mm overreamed drill holes. Allogenic, fresh-frozen (-80 degrees) cancellous bone graft was packed around the implants in six dogs. In a matched group of six other dogs, the implants were left in overreamed canals without bone graft. After six weeks the interface shear strength of grafted Ti-coated implants had significantly increased compared to the nongrafted Ti implants. However, HA coating used without bone graft was capable of enhancing the bone-implant interface shear strength to nearly the same degree. The fixation of grafted Ti- and HA-coated implants was equal. No significant difference in implant fixation was found between osteopenic and control bone. Histomorphometric evaluation of mineralizing surfaces in direct contact with the implant confirmed the results from the push-out test. Bone-implant fixation when using allogeneic fresh-frozen cancellous bone graft in osteopenic and control bone was enhanced by hydroxyapatite coating but the HA coating alone appeared to offer almost the same improvement in anchorage in 2-mm defects. Loss of bone stock around loose prosthetic implants often requires bone grafting. However, because of anatomic constraints in joint prosthetic surgery, a complete filling of defects with bone graft is difficult, and areas of gaps between bone and implant will remain. Provided mechanical stability of the prosthesis, the results reported here suggest that these areas will probably be filled early with new mineralizing bone if the prosthesis is coated with a thin layer of hydroxyapatite.     

New insight into the mechanism of hip prosthesis loosening: effect of titanium debris size on osteoblast function.

The incidence of rheumatoid arthritis and osteoarthritis is on the rise due to our expanding elderly population. Total joint arthroplasty is the most successful, prevalent treatment modality for these and other degenerative hip conditions. Despite the wide array of prosthetic devices commercially available, hip prostheses share a common problem with a gradual and then accelerating loss of bone tissue and bone-implant interface integrity, followed by implant instability and loosening. Implant failure is largely the result of inevitable wear of the device and generation of wear debris. To provide information for the development of improved prosthetic wear characteristics, we examined the effects of size-separated titanium particles on bone forming cell populations. We demonstrate unequivocally that particle size is a critical factor in the function, proliferation, and viability of bone-forming osteoblasts in vitro. In addition, we have elucidated the time-dependent distribution of the phagocytosed particles within the osteoblast, indicating an accumulation of particles in the perinuclear area of the affected cells. The report finds that particle size is a critical factor in changes in the bone formation-related functions of osteoblasts exposed to simulate wear debris, and that 1.5-4 microm titanium particles have the greatest effect on osteoblast proliferation and viability in vitro. The size of titanium particles generated through wear of a prosthetic device may be an important consideration in the development of superior implant technology.     

Osseointegrated Titanium Implants: Requirements for Ensuring a Long-Lasting, Direct Bone-to-Implant Anchorage in Man

A total of 2895 threaded, cylindrical titanium implants have been inserted into the mandible or the maxilla and 124 similar implants have been installed in the tibial, temporal or iliac bones in man for various bone restorative procedures. The titanium screws were implanted without the use of cement, using a meticulous technique aiming at osseointegration-a direct contact between living bone and implant. Thirty-eight stable and integrated screws were removed for various reasons from 18 patients. The interface zone between bone and implant was investigated using X-rays, SEM, TEM and histology. The SEM study showed a very close spatial relationship between titanium and bone. The pattern of the anchorage of collagen filaments to titanium appeared to be similar to that of Sharpey's fibres to bone. No wear products were seen in the bone or soft tissues in spite of implant loading times up to 90 months. The soft tissues were also closely adhered to the titanium implant, thereby forming a biological seal, preventing microorganism infiltration along the implant. The implants in many cases had been allowed to permanently penetrate the gingiva and skin. This caused no adverse tissue effects. An intact bone-implant interface was analyzed by TEM, revealing a direct bone-to-implant interface contact also at the electron microscopic level, thereby suggesting the possibility of a direct chemical bonding between bone and titanium. It is concluded that the technique of osseointegration is a reliable type of cement-free bone anchorage for permanent prosthetic tissue substitutes. At present, this technique is being tried in clinical joint reconstruction. In order to achieve and to maintain such a direct contact between living bone and implant, threaded, unalloyed titanium screws of defined finish and geometry were inserted using a delicate surgical technique and were allowed to heal in situ, without loading, for a period of at least 3-4 months.     

Migration of polyethylene particles around stable implants in an animal model

The aim of this study was to test the hypothesis that a tight seal between bone and implant will eliminate the avenue of particle migration around stable implants. Three types of implants were used in rabbits (polished press-fit Ti-6Al-4V or plasma-sprayed hydroxyapatite [HA]-coated Ti-6Al-4V) or doughy stage polymethyl methacrylate (PMMA). Implants were placed in the condylar notch. Each animal received an intra-articular injection of high density polyethylene (PE) particles (10(8) in 0.4 mL; mean size 4.7 microns) at 4 and 6 weeks postoperatively. Eight weeks postoperatively, peri-implant tissues were examined for PE particles and osteolysis. In all cases, intracellular PE particles were seen at the bone-implant interface and within marrow. No osteolysis was observed. Bone apposition was determined by computerized image analysis. There was no significant difference in the percentage of bone apposition (+/- SD) among the three groups of implants: Ti-6Al-4V (68% +/- 19%), HA-coated Ti-6Al-4V (70% +/- 10%), and PMMA (59% +/- 12%). These results indicate that a polished Ti-6Al-4V surface is as effective as PMMA or HA coating in limiting migration of PE particles around stable osseointegrated implants in rabbits.     

微小假体磨损颗粒诱导置入物旁骨溶解的扫描电镜观察

为比较不同人工关节微小磨损颗粒对假体－骨界面处骨整合及骨整合及骨溶解的影响,探讨假体松动的机制。方法本实验采用扫描电镜技术对钛事金、钴－铬－钼与聚乙烯（ｕｌｔｒａｈｉｇｈｍｏｌｅｃｕｌａｒｗｅｉｇｈｔｐｏｌｙｅｔｈｙｌｅｎｅ,ＵＨＭＷＰＥ）三种微小颗粒诱导的假体周围骨组织改变进行超微结构观察。结果研究发现,直径２．５μｍ的Ｔｉ－６Ａｌ－４Ｖ颗粒诱导置入物旁骨吸收或骨溶解的程度明显低于相同直径的Ｃｏ     

Particulate endocytosis mediates biological responses of human mesenchymal stem cells to titanium wear debris.

Continual loading and articulation cycles undergone by metallic (e.g., titanium) alloy arthroplasty prostheses lead to liberation of a large number of metallic debris particulates, which have long been implicated as a primary cause of periprosthetic osteolysis and postarthroplasty aseptic implant loosening. Long-term stability of total joint replacement prostheses relies on proper integration between implant biomaterial and osseous tissue, and factors that interfere with this integration are likely to cause osteolysis. Because multipotent mesenchymal stem cells (MSCs) located adjacent to the implant have an osteoprogenitor function and are critical contributors to osseous tissue integrity, when their functions or activities are compromised, osteolysis will most likely occur. To date, it is not certain or sufficiently confirmed whether MSCs endocytose titanium particles, and if so, whether particulate endocytosis has any effect on cellular responses to wear debris. This study seeks to clarify the phenomenon of titanium endocytosis by human MSCs (hMSCs), and investigates the influence of endocytosis on their activities. hMSCs incubated with commercially pure titanium particles exhibited internalized particles, as observed by scanning electron microscopy and confocal laser scanning microscopy, with time-dependent reduction in the number of extracellular particles. Particulate endocytosis was associated with reduced rates of cellular proliferation and cell-substrate adhesion, suppressed osteogenic differentiation, and increased rate of apoptosis. These cellular effects of exposure to titanium particles were reduced when endocytosis was inhibited by treatment with cytochalasin D, and no significant effect was seen when hMSCs were treated only with conditioned medium obtained from particulate-treated cells. These findings strongly suggest that the biological responses of hMSCs to wear debris are triggered primarily by the direct endocytosis of titanium particulates, and not mediated by secreted soluble factors. In this manner, therapeutical approaches that suppress particle endocytosis could reduce the bioreactivity of hMSCs to particulates, and enhance long-term orthopedic implant prognosis by minimizing wear-debris periprosthethic osteolysis.     

Tissue reactions to titanium endoprostheses. Autopsy studies in four cases

Four cementless prosthetic hip implants of Ti-6Al-4V-alloy with and without longitudinal grooves and Al2O2 ceramic ball heads, with implant periods of 3, 4, 5, and 10 months, were sectioned and examined histologically in undecalcified thin ground sections. Especially on the medial and lateral sides of the prostheses, there was direct bone-to-metal contact without interposed connective tissue, spreading to the dorsal and ventral areas of the prosthesis shaft, which was considered osseointegration. This is based mainly on the technique of implantation with primary stability in the cortical bone by press-fit and on the bioinertness of the titanium alloy. Ungrooved prosthesis areas seem to favor bone growth at the shaft. The secondary bone ring, occurring on the dorsal and ventral areas of the prosthesis, with evidence of further bone remodeling with the passage of time, indicates that osseointegration is a dynamic process that continues to improve prosthetic stability.     

Osteolysis in alloarthroplasty of the hip. The role of bone cement fragmentation

Movement at the interface between bone and cement and fractures of the cement can cause fragmentation of the polymethylmethacrylate (PMMA) bone cement implant. In order to obtain further information about the effect of PMMA fragments on the surrounding tissue and the role of such particles in the development of bone resorption, the authors investigated 17 patients with cemented total hip endoprostheses showing osteolysis and implant loosening in the femoral shaft with (Group B) and without (Group A) involvement of the acetabulum. The roentgenographic follow-up examinations revealed an initially slow and later more rapid extension of the endosteal bone erosions, with a predilection for the tip of the stem, the lesser trochanter, and laterally for the middle of the stem. At revision surgery, tissue samples were taken from the joint capsule and the bone-cement interface, in particular from the osteolysis in the femoral shaft and the acetabulum. The tissue samples were processed for histology, microscopically examined, and semiquantitatively evaluated. The retrieved devices were also carefully inspected. Large foreign-body granulomas were found at the bone-cement interface and in the joint capsule. Histiocytes and foreign-body giant cells stored particles of PMMA and polyethylene, of which fragmented bone cement predominated. Granulomatous tissue invaded bone canals and marrow spaces and induced resorption of the surrounding bone. In four cases in Group A, tissue from the osteolysis contained only fragmented bone cement, demonstrating that PMMA particles alone may be responsible for triggering focal bone resorption. Osteolysis seems to begin at the site where disintegration of bone cement begins. In cases in which polyethylene particles were found in the tissue in addition to fragmented bone cement, wear from the ultrahigh molecular weight polyethylene socket has been increased by entrapment of PMMA particles between the joint surfaces. Thus, fragmentation of bone cement and abrasion of polyethylene enhance each other. Bone cement particles promote polyethylene wear, which in turn promotes granuloma formation, bone resorption, and subsequent bone cement disintegration.     

Local delivery of mutant CCL2 protein‐reduced orthopaedic implant wear particle‐induced osteolysis and inflammation in vivo

Total joint replacement (TJR) has been widely used as a standard treatment for late‐stage arthritis. One challenge for long‐term efficacy of TJR is the generation of ultra‐high molecular weight polyethylene wear particles from the implant surface that activates an inflammatory cascade which may lead to bone loss, prosthetic loosening and eventual failure of the procedure. Here, we investigate the efficacy of local administration of mutant CCL2 proteins, such as 7ND, on reducing wear particle‐induced inflammation and osteolysis in vivo using a mouse calvarial model. Mice were treated with local injection of 7ND or phosphate buffered saline (PBS) every other day for up to 14 days. Wear particle‐induced osteolysis and the effects of 7ND treatment were evaluated using micro‐CT, histology, and immunofluorescence staining. Compared with the PBS control, 7ND treatment significantly decreased wear particle‐induced osteolysis, which led to a higher bone volume fraction and bone mineral density. Furthermore, immunofluorescence staining showed 7ND treatment decreased the number of recruited inflammatory cells and osteoclasts. Together, our results support the feasibility of local delivery of 7ND for mitigating wear particle‐induced inflammation and osteolysis, which may offer a promising strategy for extending the life time of TJRs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:58–64, 2016.